Transforming growth factor-β and toll-like receptor-4 polymorphisms are not associated with fibrosis in haemochromatosis

AIM:To investigate the role of genetic polymorphisms in the progression of hepatic fibrosis in hereditary haemochromatosis.METHODS:A cohort of 245 well-characterised C282Y homozygous patients with haemochromatosis was studied,with all subjects having liver biopsy data and DNA available for testing.This study assessed the association of eight single nucleotide polymorphisms(SNPs)in a total of six genes including toll-like receptor 4(TLR4),transforming growth factor-beta(TGF-β),oxoguanine DNA glycosylase,monocyte chemoattractant protein 1,chemokine C-C motif receptor 2 and interleukin-10 with liver disease severity.Genotyping was performed using high resolution melt analysis and sequencing.The results were analysed in relation to the stage of hepatic fibrosis in multivariate analysis incorporating other cofactors including alcohol consumption and hepatic iron concentration.RESULTS:There were significant associations between the cofactors of male gender(P=0.0001),increasing age(P=0.006),alcohol consumption(P=0.0001),steatosis(P=0.03),hepatic iron concentration(P<0.0001)and the presence of hepatic fibrosis.Of the candidate gene polymorphisms studied,none showed a significant association with hepatic fibrosis in univariate or multivariate analysis incorporating cofactors.We also specifically studied patients with hepatic iron loading above threshold levels for cirrhosis and compared the genetic polymorphisms between those with no fibrosis vs cirrhosis however there was no significant effect from any of the candidate genes studied.Importantly,in this large,well characterised cohort of patients there was no association between SNPs for TGF-βor TLR4and the presence of fibrosis,cirrhosis or increasing fibrosis stage in multivariate analysis.CONCLUSION:In our large,well characterised group of haemochromatosis subjects we did not demonstrate any relationship between candidate gene polymorphisms and hepatic fibrosis or cirrhosis.

Association between PPARG genetic polymorphisms and ischemic stroke risk in a northern Chinese Han population: a case-control study

Two common polymorphisms of the peroxisome proliferator-activated receptor gamma(PPARG) gene, rs1801282 and rs3856806, may be important candidate gene loci affecting the susceptibility to ischemic stroke. This case-control study sought to identify the relationship between these two single-nucleotide polymorphisms and ischemic stroke risk in a northern Chinese Han population. A total of 910 ischemic stroke participants were recruited from the First Hospital of China Medical University, Shenyang, China as a case group, of whom 895 completed the study. The 883 healthy controls were recruited from the Health Check Center of the First Hospital of China Medical University, Shenyang, China. All participants or family members provided informed consent. The study protocol was approved by the Ethics Committee of the First Hospital of China Medical University, China on February 20, 2012(approval No. 2012-38-1). The protocol was registered with the Chinese Clinical Trial Registry(registration number: ChiCTR-COC-17013559). Plasma genomic DNA was extracted from all participants and analyzed for rs1801282 and rs3856806 single nucleotide polymorphisms using a SNaPshot Multiplex sequencing assay. Odds ratios(ORs) and 95% confidence intervals(CIs) were calculated using unconditional logistic regression to estimate the association between ischemic stroke and a particular genotype. Results demonstrated that the G allele frequency of the PPARG gene rs1801282 locus was significantly higher in the case group than in the control group(P < 0.001). Individuals carrying the G allele had a 1.844 fold increased risk of ischemic stroke(OR = 1.844, 95% CI: 1.286–2.645, P < 0.001). Individuals carrying the rs3856806 T allele had a 1.366 fold increased risk of ischemic stroke(OR = 1.366, 95% CI: 1.077–1.733, P = 0.010). The distribution frequencies of the PPARG gene haplotypes rs1801282-rs3856806 in the control and case groups were determined. The frequency of distribution in the G-T haplotype case group was significantly higher than that in the control group. The risk of ischemic stroke increased to 2.953 times in individuals carrying the G-T haplotype(OR = 2.953, 95% CI: 2.082–4.190, P < 0.001). The rs1801282 G allele and rs3856806 T allele had a multiplicative interaction(OR = 3.404, 95% CI: 1.631–7.102, P < 0.001) and additive interaction(RERI = 41.705, 95% CI: 14.586–68.824, AP = 0.860;95% CI: 0.779–0.940;S = 8.170, 95% CI: 3.772–17.697) on ischemic stroke risk, showing a synergistic effect. Of all ischemic stroke cases, 86% were attributed to the interaction of the G allele of rs1801282 and the T allele of rs3856806. The effect of the PPARG rs1801282 G allele on ischemic stroke risk was enhanced in the presence of the rs3856806 T allele(OR = 8.001 vs. 1.844). The effect of the rs3856806 T allele on ischemic stroke risk was also enhanced in the presence of the rs1801282 G allele(OR = 2.546 vs. 1.366). Our results confirmed that the G allele of the PPARG gene rs1801282 locus and the T allele of the rs3856806 locus may be independent risk factors for ischemic stroke in the Han population of northern China, with a synergistic effect between the two alleles.

PNPLA3 I148M polymorphism and progressive liver disease

The 148 Isoleucine to Methionine protein variant(I148M)of patatin-like phospholipase domain-containing 3(PNPLA3),a protein is expressed in the liver and is involved in lipid metabolism,has recently been identified as a major determinant of liver fat content.Several studies confirmed that the I148M variant predisposes towards the full spectrum of liver damage associated with fatty liver:from simple steatosis to steatohepatitis and progressive fibrosis.Furthermore,the I148M variant represents a major determinant of progression of alcohol related steatohepatitis to cirrhosis,and to influence fibrogenesis and related clinical outcomes in chronic hepatitis C virus hepatitis,and possibly chronic hepatitis B virus hepatitis,hereditary hemochromatosis and primary sclerosing cholangitis.All in all,studies suggest that the I148M polymorphism may represent a general modifier of fibrogenesis in liver diseases.Remarkably,the effect of the I148M variant on fibrosis was independent of that on hepatic steatosis and inflammation,suggesting that it may affect both the quantity and quality of hepatic lipids and the biology of non-parenchymal liver cells besides hepatocytes,directly promoting fibrogenesis.Therefore,PNPLA3 is a key player in liver disease progression.Assessment of the I148M polymorphism will possibly inform clinical practice in the future,whereas the determination of the effect of the 148M variant will reveal mechanisms involved in hepatic fibrogenesis.

Single Nucleotide Polymorphisms (SNPs) of URAT1 (rs7932775) and ABCG2 (rs3825016) on Chronic Kidney Disease Patients with Hyperuricemia

Background: More and more chronic kidney disease (CKD) patients are accompanied with hyperuricaemia. As is known, hyperuricaemia is an independent hazard of both cardiovascular diseases (CVD) and chronic kidney diseases. We aim at identifying Single Nucleotide Polymorphism (SNP) difference of hURAT1 (rs7932775) and ABCG2 (rs3825016) on CKD patient with hyperuricemia and/or gout. Methods: All forty-two CKD patients were divided into two groups: hyperuricemia, and control group. 24 hours urine sample and serum were prepared for testing biochemistry parameters. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method is used to analyze hURAT1 and ABCG2 single nucleotide polymorphisms in different groups. Results: 17 patients have CT SNP of hURAT1 (rs7932775) and 13 patients have CT SNP of ABCG2 (rs3825016) in hyperuricemia group, while only 5 persons and 6 persons have the same mutations in control group respectively. 7 patients have CT SNP of both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group, while only 2 persons have the same mutations in control group. CT mutation rates of hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 60.7% (17/28) and 50% (13/28) respectively, higher than that of control group (35.7% (5/14) and 42.8% (6/14)). What is more, Double SNP mutations in both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 25% (7/28), higher than that of control group (14.2%, 2/14). Conclusion: There are higher mutation rates of CT SNP in hURAT1 (rs7932775) and/or ABCG2 (rs3825016) in hyperuricemia group. We can conclude that hyperuricemia is a high risk factor in progress of CKD, which is necessary to take measures of decreasing serum uric acid to delay CKD progress.

Fibroblast growth factor receptor 4 single nucleotide polymorphism Gly388Arg in head and neck carcinomas

BACKGROUND Head and neck squamous cell carcinoma(HNSCC) is considered to be a progressive disease resulting from alterations in multiple genes regulating cell proliferation and differentiation like receptor tyrosine kinases(RTKs) and members of the fibroblast growth factor receptors(FGFR)-family. Singlenucleotide polymorphism(SNP) Arg388 of the FGFR4 is associated with a reduced overall survival in patients with cancers of various types. We speculate that FGFR4 expression and SNP is associated with worse survival in patients with HSNCC.AIM To investigate the potential clinical significance of FGFR4 Arg388 in the context of tumors arising in HNSCC, a comprehensive analysis of FGFR4 receptor expression and genotype in tumor tissues and correlated results with patients' clinical data in a large cohort of patients with HNSCC was conducted.METHODS Surgical specimens from 284 patients with HNSCC were retrieved from the Institute of Pathology at the Ludwig-Maximilian-University in Germany.Specimens were analyzed using immunohistochemistry and polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). The expression of FGFR4 was analyzed in 284 surgical specimens of HNSCC using immunohistochemstry. FGFR4 polymorphism was detected by PCR-RFLP.Patients' clinical data with a minimum follow-up of 5 years were statistically evaluated with a special emphasis on survival analysis employing Kaplan-Meier estimator and Cox regression analysis.RESULTS Concerning the invasive tumor areas the intensity of the FGFR4 expression was evaluated in a four-grade system: no expression, low expression, intermediate and high expression. FGFR4 expression was scored as "high"(+++) in 74(26%),"intermediate"(++) in 103(36.3%), and "low"(+) in 107(36.7%) cases. Analyzing the FGFR4 mutation it was found in 96 tumors(33.8%), 84 of them(29.6%) having a heterozygous and 12(4.2%) homozygous mutated Arg388 allele. The overall frequency concerning the mutant alleles demonstrated 65% vs 34% mutated alleles in general. FGFR4 Arg388 was significantly associated with advanced tumor stage(P < 0.004), local metastasis(P < 0.0001) and reduced disease-free survival(P < 0.01). Furthermore, increased expression of FGFR4 correlated significantly with worse overall survival(P < 0.003).CONCLUSION In conclusion, the FGFR4 Arg388 genotype and protein expression of FGFR4 impacts tumor progression in patients with HNSCC and may present a useful target within a multimodal therapeutic intervention.

Association of endothelial nitric oxide synthase gene T-786C promoter polymorphism with gastric cancer

AIM: To investigate the role of endothelial nitric oxide synthase-786 T > C promoter polymorphism in the etiology of gastric cancer(GC). METHODS: A total of 150 GC patients and 150 control subjects were included in the study. The information on demographic features was elicited with an informed consent from all the patients and control subjects using a structured questionnaire. Helicobacter pylori(H. pylori) infectivity status was tested in antral biopsies from all the subjects by rapid urease test following the method of Vaira et al. Genomic DNA was isolated from whole blood samples following the salting out method of Lahiri et al. Genotype analysis of the rs2070744 polymorphism was carried out by allele-specific polymerase chain reaction method. The genotypes were determined based on the appearance of bands on an agarose gel stained with ethidium bromide under ultraviolet gel documentation with the help of 100 bp ladder. Odds ratios and corresponding 95%CIs were determined using java stat online software. RESULTS: There was a significant difference in the distribution of C allele(C vs T; P = 0.000, OR = 5.038) in patient group compared to the control subjects exhibiting a fivefold increased risk for GC. When the T/T and C/C genotypes were compared, there was an enhanced GC risk for individuals with C/C genotype(T/T vs C/C; P = 0.000). Among the demographic factors, smoking and alcoholism were the common risk factors in patients compared to the control subjects(P < 0.05). Patients with smoking and alcoholism developed cancer even in heterozygous T/C condition(smoking: P = 0.020 and alcoholism: P = 0.005). Individuals with H. pylori infection showed seven fold increased risk for cancer. All the patients with C/C genotype revealed a significant association between H. pylori infection and GC. Among the patients 2.4% of them revealed familial incidence of GC. No significant difference was noticed between cases and controls with regard to consanguinity(P = 0.473).CONCLUSION: The Present data suggest that eN OS-786 C/C genotype and C allele may be considered as potential risk factors in patients with GC.

Antibiotic-Resistant Bacterial Group in Field Soil Evaluated by a Newly Developed Method Based on Restriction Fragment Length Polymorphism Analysis

Spreading of antibiotic resistant bacteria into environment is becoming a major public health problem, implicating affair of the indirect transmission of antibiotic resistant bacteria to human through drinking water, or vegetables, or daily products. Until now, the risk of nosocomial infection of antibiotic resistant bacteria has mainly been evaluated using clinical isolates by phenotypic method. To evaluate a risk of community-acquired infection of antibiotic resistant bacteria, a new method has been developed based on PCR-RFLP without isolation. By comparing restriction fragment lengths of the 16S rDNA gene from bacterial mixture grown under antibiotic treatment to those simulated from the DNA sequence, bacterial taxonomies were elucidated using the method of Okuda and Watanabe [1] [2]. In this study, taxonomies of polymyxin B resistant bacteria group in field soils, paddy field with organic manure and upland field without organic manure were estimated without isolation. In the both field soils, the major bacteria grown under the antibiotic were B. cereus group, which had natural resistance to this antibiotic. In field applied with organic manure, Prevotella spp., and the other Cytophagales, which were suggested to be of feces origin and to acquire resistance to the antibiotic, were detected. When numbers of each bacterial group were roughly estimated by the most probable number method, B. cereus group was enumerated to be 3.30 × 106 MPN/g dry soil in paddy field soil and 1.32 × 106 MPN/g dry soil in upland filed. Prevotella spp. and the other Cytophagales in paddy field were enumerated to be 1.31 × 106 MPN, and 1.07 × 106 MPN·g-1 dry soil.

GSTM1,GSTT1,GSTP1 and CYP1A1 genetic polymorphisms and susceptibility to esophageal cancer in a French population:Different pattern of squamous cell carcinoma and adenocarcinoma

AIM:To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma(SCC)and esophageal adenocarcinoma(ADC)in a high risk area of northwest of France. METHODS:A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYPIAI*2C and GSTP1 exon 7 Val alleles,GSTMI*2/*2 and GSTTl *2/*2 null genotypes).A total of 79 esophageal cancer cases and 130 controls were recruited. RESULTS:GSTMI*2/*2 and CYPIAI*IA/*2C genotype frequencies were higher among squamous cell carcinomas at a level dose to statistical significance(OR =1.83,95% CI 0.88-3.83,P=0.11;OR=3.03,95% CI 0.93-9.90,P=0.07, respectively).For GSTP1 polymorphism,no difference was found between controls and cases,whatever their histological status.Lower frequency of GSTT1 deletion was observed in ADC group compared to controls with a statistically significant difference(OR=13.31,95% CI 1.66-106.92,P<0.01). CONCLUSION:In SCC,our results are consistent with the strong association of this kind of tumour with tobacco exposure.In ADC,our results suggest 3 distinct hypotheses: (1)activation of exogenous procarcinogens,such as small halogenated compounds by GSTT1;(2)contribution of GSTT1 to the inflammatory response of esophageal mucosa,which is known to be a strong risk factor for ADC, possibly through leukotriene synthesis;(3)higher sensitivity to the inflammatory process associated with intracellular depletion of glutathione.

Association between Gene Polymorphisms and SNP-SNP Interactions of the Matrix Metalloproteinase 2 Signaling Pathway and the Risk of Vascular Senescence

Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cf PWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling.Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions.Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.

GSTT1,GSTM1 and CYP2E1 genetic polymorphisms in gastric cancer and chronic gastritis in a Brazilian population

AIM:To test the hypothesis that,in the Southeastern Brazilian population,the GSTT1,GSTM1 and CYP2E1 polymorphisms and putative risk factors are associated with an increased risk for gastric cancer. METHODS:We conducted a study on 100 cases of gastric cancer (GC),100 cases of chronic gastritis (CG),and 150 controls (C).Deletion of the GSTT1 and GSTM1 genes was assessed by multiplex PCR.CYP2E1/Pst1 genotyping was performed using a PCR-RFLP assay. RESULTS:No relationship between GSTT1/GSTM1 deletion and the c1/c2 genotype of CYP2E1 was observed among the three groups.However,a significant difference between CG and C was observed,due to a greater number of GSTT1/GSTM1 positive genotypes in the CG group.The GSTT1 null genotype occurred more frequently in Negroid subjects,and the GSTM1 null genotype in Caucasians,while the GSTM1 positive genotype was observed mainly in individuals with chronic gastritis infected with H pylori. CONCLUSION:Our findings indicate that there is no obvious relationship between the GSTT1,GSTM1 and CYP2E1 polymorphisms and gastric cancer.

Taq1B CETP Polymorphism and Cardiovascular Risk in an Endogamous Pop-ulation of Diabetic Men: A Study in Santa Rosa Del Conlara, San Luis, Argentina

Objectives: Type 2 diabetes mellitus (T2DM) patients are at increased risk of cardiovascular diseases (CVDs). Several polymorphisms in the cholesterol ester transfer protein (CETP) gene have been reported. The aim of this study was to determine the distribution and effect of the Taq1B polymorphism in the CETP gene on clinical and biochemical indicators of CVD risk in a population of endogamous-T2DM men. Methods: 102 men (57.5 ± 9.3 years old) inhabitants of Santa Rosa del Conlara, San Luis, Argentina, were recruited and assigned into two groups (22 control and 80 T2DM). Further, these two groups were subdivided according to their Taq1B CETP gene genotypes (i.e., B1B1, B1B2 and B2B2). Clinical and fasting-plasma biochemical indicators of CVD risk were measured and their association with the B1 allele was determined. Results: Compared to control, T2DM men had more central obesity, hypertension, atherogenic index, insulin resistance and poorly controlled diabetes. Compared to T2DM men having the B2 allele, those T2DM men having the B1 allele have increased risk of CVD as assessed by systolic blood pressure (156 ± 16.0 vs 135.8 ± 19.2, p = 0.015), atherogenic index (6.15 ± 1.3 vs 4.4 ± 0.7, p = 0.0008), HDL-c levels (38.9 ± 5.3 vs 64.4 ± 8.2, p ± 3.0 vs 2.4 ± 0.78, p = 0.004). Interestingly, only body mass index (r = ﹣0.559, p = 0.01) and HDL-c concentration (r = ﹣0.492, p = 0.02) negatively correlated with CVD risk in the endogamous population of B1B1 and B1B2 T2DM men. Conclusion: The B1 allele of the CETP gene predicts cardiovascular complications in an endogamous population of T2DM men.

Distribution of gene polymorphisms associated with aspirin antiplatelet in the Han NSTEMI population

Objective:To analyze the genotype and allele distribution characteristics of GPⅢa PLA2(rs5918),PEAR1(rs12041331),and PTGS1(rs10306114)genes related to the antiplatelet pharmacological effects of aspirin,providing reference for individualized treatment of Chinese Han NSTEMI patients.Methods:A total of 107 Han patients with NSTEMI in Beijing Luhe Hospital affiliated to Capital Medical University from January 2016 to December 2022 were selected as the research subjects.The genotypes of GPⅢa PLA2(rs5918),PEAR1(rs12041331)and PTGS1(rs10306114)were detected by fluorescence staining in situ hybridization.The frequency distribution and allele distribution of genotype were analyzed.The results were analyzed whether there were statistical differences in the distribution of related alleles between the Han NSTEMI population and some populations in the 1000 Genomes database.Results:In the Han NSTEMI population,the genotype frequencies of GPⅢa PLA2(rs5918)locus were TT 97.20%,TC 2.80%and CC 0%,the allele frequencies were T 98.60%and C 1.40%.The genotype frequencies of PEAR1(rs12041331)locus were GG 42.06%,GA 44.86%and AA 13.08%,the allele frequencies were G 64.49%and A 35.51%.The genotypes at the PTGS1(rs10306114)locus were all AA(100%),no AG or GG genotype was found.Conclusion:In the NSTEMI population of Han nationality,the mutation at GPⅢa PLA2(rs5918)site related to aspirin antiplatelet pharmacology is rare,and there is no mutation at PTGS1(rs10306114)site.Wild homozygotes are dominant in these two gene loci,while mutations in PEAR1(rs12041331)are more common.Some of the findings in this study are similar to those in previous reports or other populations included in the relevant database;however,some results differ from previous reports or other populations。

Tumor necrosis factor-α-G308A polymorphism is associated with liver pathological changes in hepatitis C virus patients

AIM To investigate the association of tumor necrosis factor alpha(TNFα)-G308 A polymorphism with different liver pathological changes in treatment-na?ve Egyptian patients infected with hepatitis C virus(HCV) genotype 4.METHODS This study included 180 subjects,composed of 120 treatment-na?ve chronic HCV patients with different fibrosis grades(F0-F4) and 60 healthy controls. The TNFα-G308 A region was amplified by PCR and the different genotypes were detected by restriction fragment length polymorphism analysis. The TNFα protein was detected by enzyme-linked immunosorbent assay. The influence of different TNFα-G308 A genotypes on TNFα expression and liver disease progression were statistically analyzed. The OR and 95%CI were calculated to assess the relative risk confidence.RESULTS Current data showed that the TNFα-G308 A SNP frequency was significantly different between controls and HCV infected patients(P = 0.001). Both the AA genotype and A allele were significantly higher in late fibrosis patients(F2-F4,n = 60) than in early fibrosis patients(F0-F1,n = 60)(P = 0.05,0.04 respectively). Moreover,the GA or AA genotypes increased the TNFα serum level greater than the GG genotype(P = 0.002). The results showed a clear association between severe liver pathological conditions(inflammation,steatosis and fibrosis) and(GA + AA) genotypes(P = 0.035,0.03,0.04 respectively). The stepwise logistic regression analysis showed that the TNFα genotypes(GA + AA) were significantly associated with liver inflammation(OR = 3.776,95%CI: 1.399-10.194,P = 0.009),severe steatosis(OR = 4.49,95%CI: 1.441-14.0,P = 0.010) and fibrosis progression(OR = 2.84,95%CI: 1.080-7.472,P = 0.034). Also,the A allele was an independent risk factor for liver inflammation(P = 0.003),steatosis(P = 0.003) and fibrosis(P = 0.014). CONCLUSION TNFα SNP at nucleotide-308 represents an important genetic marker that can be used for the prognosis of different liver pathological changes in HCV infected

Association of GTF2IRD1–GTF2I polymorphisms with neuromyelitis optica spectrum disorders in Han Chinese patients

Variants at the GTF2I repeat domain containing 1(GTF2IRD1)–GTF2I locus are associated with primary Sj?gren's syndrome, systemic lupus erythematosus, and rheumatoid arthritis. Numerous studies have indicated that this susceptibility locus is shared by multiple autoimmune diseases. However, until now there were no studies of the correlation between GTF2IRD1–GTF2I polymorphisms and neuromyelitis optica spectrum disorders(NMOSD). This case control study assessed this association by recruiting 305 participants with neuromyelitis optica spectrum disorders and 487 healthy controls at the Department of Neurology, from September 2014 to April 2017. Peripheral blood was collected, DNA extracteds and the genetic association between GTF2IRD1–GTF2I polymorphisms and neuromyelitis optica spectrum disorders in the Chinese Han population was analyzed by genotyping. We found that the T allele of rs117026326 was associated with an increased risk of neuromyelitis optica spectrum disorders(odds ratio(OR) = 1.364, 95% confidence interval(CI) 1.019–1.828; P = 0.037). This association persisted after stratification analysis for aquaporin-4 immunoglobulin G antibodies(AQP4-IgG) positivity(OR = 1.397, 95% CI 1.021–1.912; P = 0.036) and stratification according to coexisting autoimmune diseases(OR = 1.446, 95% CI 1.072–1.952; P = 0.015). Furthermore, the CC genotype of rs73366469 was frequent in AQP4-IgG-seropositive patients(OR = 3.15, 95% CI 1.183–8.393, P = 0.022). In conclusion, the T allele of rs117026326 was associated with susceptibility to neuromyelitis optica spectrum disorders, and the CC genotype of rs73366469 conferred susceptibility to AQP4-IgG-seropositivity in Han Chinese patients. The protocol was approved by the Ethics Committee of West China Hospital of Sichuan University, China(approval number: 2016-31) on March 2, 2016.

Role of genetic polymorphisms in hepatitis C virus chronic infection

AIM: To analyze the host genetics factors influencing the clinical course and the response to antiviral treatment in patients with chronic hepatitis C(CHC).METHODS: We conducted an electronic search on the Pub Med and MEDLINE(2000-2014) databases and Cochrane library(2000-2014). A total of 73 articles were retrieved and their data were extensively evaluated and discussed by the authors and then analyzed in this review article.RESULTS: Several studies associated polymorphisms in the interleukin 28 B gene on chromosome 19(19q13.13) with a spontaneous viral clearance in acute hepatitis C and with the response to pegylated interferon(PegIFN)-based treatment in chronic hepatitis C patients. Other investigations demonstrated that inosine triphosphate pyrophosphatase genetic variants protect hepatitis C virus-genotype-1 CHC patients from ribavirin-induced anemia, and other studies that a polymorphism in the patatin-like phospholipase domain-containing protein 3 was associated with hepatic steatosis in CHC patients. Although not conclusive, some investigations suggested that the vitamin D-associated polymorphisms play an important role in the achievement of sustained virologic response in CHC patients treated with Peg-IFN-based antiviral therapy. Several other polymorphisms have been investigated to ascertain their possible impact on the natural history and on the response to treatment in patients with CHC, but the data are preliminary and warrant confirmation. CONCLUSION: Several genetic polymorphisms seem to influence the clinical course and the response to antiviral treatment in patients with CHC, suggesting individualized follow up and treatment strategies.

Bacterial Groups Concerned with Maturing Process in Manure Production Analyzed by a Method Based on Restriction Fragment Length Polymorphism Analysis

Composting is a biological aerobic decomposition process consisted from different phases. Although the Japanese Standards for manure recommended that it took at least 6 months to complete the maturing phase, there was no reliable ground. In order to find out shortening method of the maturing phase, the microorganisms concerned with a progress of the maturing was determined by using the most probable number method (MPN) and PCR-RFLP of the 16S rDNA, which was found effective to provide numbers and taxonomy of polymyxin B resistant bacterial groups in the former paper [1]. Compared to the numbers after thermophilic phase, those of Actinobacteria, δ-proteobacteria, and the other gram negative bacteria increased to 50 times, 20 times, and 105 times, respectively, after maturing phase, while those of Bacillus spp., and α and β-proteobacteria decreased to 1/10, and 1/105 after maturing phase. Numbers of the other Fumicutes, and γ-proteobacteria remained in the same revel. Actinobacteria, δ-proteobacteria, and the other gram negative bacteria might be concerned with a progress of the maturing phase, because these bacterial groups were detected and enumerated due to their proliferation ability. Although number of Acitinobacteria might be underestimated because of a PCR bias, the method was found effective for the purpose to monitor bacteria actively proliferated in culture medium.

hOGG1 Ser326Cys polymorphism modifies the significance of the environmental risk factor for colon cancer

AIM:To determine the association of hOGG1 (8-oxoguanine glycosylase I,OGG1) polymorphism of Ser326Cys substitution with colon cancer risk and possible interaction with known environmental risk factors. METHODS:A case-control study with 125 colon cancer cases and 247 controls was conducted, RESULTS:There was no major difference in Ser326Cys genotype distribution between cases and controls.The meat intake tended to increase the odds ratio for colon cancer with an OR of 1.72 (95 % confidence interval;CI=1.12-2.76). Such tendency was more prominent in Cys/Cys carriers (OR=4.31,95 % CI=1.64-11.48),but meat intake was not a significant risk factor for colon cancer in Ser/Ser or Ser/ Cys carriers.The OR for colon cancer was elevated with marginal significance in smokers who were Cys/Cys carriers (OR=2.75,95 % CI=1.07-7.53) but not in Ser/Ser or Ser/ Cys carriers. CONCLUSION:These results suggest that the hOGG1 Ser326Cys polymorphism is probably not a major contributor to individual colon cancer susceptibility overall,but the Cys/ Cys genotype may alter the impact of some environmental factors on colon cancer development.

KCNQ1 rs2237895 gene polymorphism increases susceptibility to type 2 diabetes mellitus in Asian populations

BACKGROUND The association of single nucleotide polymorphism of KCNQ1 gene rs2237895 with type 2 diabetes mellitus(T2DM)is currently controversial.It is unknown whether this association can be gene realized across different populations.AIM To determine the association of KCNQ1 rs2237895 with T2DM and provide reliable evidence for genetic susceptibility to T2DM.METHODS We searched PubMed,Embase,Web of Science,Cochrane Library,Medline,Baidu Academic,China National Knowledge Infrastructure,China Biomedical Literature Database,and Wanfang to investigate the association between KCNQ1 gene rs2237895 and the risk of T2DM up to January 12,2022.Review Manager 5.4 was used to analyze the association of the KCNQ1 gene rs2237895 polymorphism with T2DM and to evaluate the publication bias of the selected literature.RESULTS Twelve case–control studies(including 11273 cases and 11654 controls)met our inclusion criteria.In the full population,allelic model[odds ratio(OR):1.19;95%confidence interval(95%CI):1.09–1.29;P<0.0001],recessive model(OR:1.20;95%CI:1.11–1.29;P<0.0001),dominant model(OR:1.27.95%CI:1.14–1.42;P<0.0001),and codominant model(OR:1.36;95%CI:1.15–1.60;P=0.0003)(OR:1.22;95%CI:1.10–1.36;P=0.0002)indicated that the KCNQ1 gene rs2237895 polymorphism was significantly correlated with susceptibility to T2DM.In stratified analysis,this association was confirmed in Asian populations:allelic model(OR:1.25;95%CI:1.13–1.37;P<0.0001),recessive model(OR:1.29;95%CI:1.11–1.49;P=0.0007),dominant model(OR:1.35;95%CI:1.20–1.52;P<0.0001),codominant model(OR:1.49;95%CI:1.22–1.81;P<0.0001)(OR:1.26;95%CI:1.16–1.36;P<0.0001).In non-Asian populations,this association was not significant:Allelic model(OR:1.06,95%CI:0.98–1.14;P=0.12),recessive model(OR:1.04;95%CI:0.75–1.42;P=0.83),dominant model(OR:1.06;95%CI:0.98–1.15;P=0.15),codominant model(OR:1.08;95%CI:0.82–1.42;P=0.60.OR:1.15;95%CI:0.95–1.39;P=0.14).CONCLUSION KCNQ1 gene rs2237895 was significantly associated with susceptibility to T2DM in an Asian population.Carriers of the C allele had a higher risk of T2DM.This association was not significant in non-Asian populations.

Importance of genetic polymorphisms in liver transplantation outcomes

Although,liver transplantation serves as the only curative treatment for patients with end-stage liver diseases,it is burdened with complications,which affect survival rates.In addition to clinical risk factors,contribution of recipient and donor genetic prognostic markers has been extensively studied in order to reduce the burden and improve the outcomes.Determination of single nucleotide polymorphisms(SNPs)is one of the most important tools in development of personalized transplant approach.To provide a better insight in recent developments,we review the studies published in the last three years that investigated an association of recipient or donor SNPs with most common issues in liver transplantation:Acute cellular rejection,development of new-onset diabetes mellitus and non-alcoholic fatty liver disease,hepatocellular carcinoma recurrence,and tacrolimus concentration variability.Reviewed studies confirmed previously established SNP prognostic factors,such as PNPLA3 rs738409 for nonalcoholic fatty liver disease development,or the role of CYP3A5 rs776746 in tacrolimus concentration variability.They also identified several novel SNPs,with a reasonably strong association,which have the potential to become useful predictors of post-transplant complications.However,as the studies were typically conducted in one center on relatively low-to-moderate number of patients,verification of the results in other centers is warranted to resolve these limitations.Furthermore,of 29 reviewed studies,28 used gene candidate approach and only one implemented a genome wide association approach.Genome wide association multicentric studies are needed to facilitate the development of personalized transplant medicine.

Interaction between catechol-O-methyltransferase Val/Met polymorphism and cognitive reserve for negative symptoms in schizophrenia

BACKGROUND Cognitive reserve(CR)and the catechol-O-methyltransferase(COMT)Val/Met polymorphism are reportedly linked to negative symptoms in schizophrenia.However,the regulatory effect of the COMT genotype on the relationship between CR and negative symptoms is still unexamined.AIM To investigate whether the relationship between CR and negative symptoms could be regulated by the COMT Val/Met polymorphism.METHODS In a cross-sectional study,54 clinically stable patients with schizophrenia underwent assessments for the COMT genotype,CR,and negative symptoms.CR was estimated using scores in the information and similarities subtests of a short form of the Chinese version of the Wechsler Adult Intelligence Scale.RESULTS COMT Met-carriers exhibited fewer negative symptoms than Val homozygotes.In the total sample,significant negative correlations were found between negative symptoms and information,similarities.Associations between information,similarities and negative symptoms were observed in Val homozygotes only,with information and similarities showing interaction effects with the COMT genotype in relation to negative symptoms(information,β=-0.282,95%CI:-0.552 to-0.011,P=0.042;similarities,β=-0.250,95%CI:-0.495 to-0.004,P=0.046).CONCLUSION This study provides initial evidence that the association between negative symptoms and CR is under the regulation of the COMT genotype in schizophrenia.