Association of TNF-α-238G/A and 308 G/A Gene Polymorphisms with Pulmonary Tuberculosis among Patients with Coal Worker’s Pneumoconiosis

Objectives Tumor necrosis factor-α （TNF-α） may play an important role in host＇s immune response to mycobacterium tuberculosis （M. tuberculosis） infection. This study was to investigate the association of TNF-α gene polymorphism with pulmonary tuberculosis （TB） among patients with coal worker＇s pneumoconiosis （CWP）. Methods A case-control study was conducted in 113 patients with confirmed CWP complicated with pulmonary TB and 113 non-TB controls with CWP. They were matched in gender, age, job, and stage of pneumoconiosis. All participants were interviewed with questionnaires and their blood specimens were collected for genetic determination with informed consent. The TNF-α gene polymorphism was determined with polymerase chain reaction of restriction fragment length polymorphism （PCR-RFLP）. Frequency of genotypes was assessed for Hardy-Weinberg equilibrium by chi-square test or Fisher＇s exact probability. Factors influencing the association of individual susceptibility with pulmonary TB were evaluated with logistic regression analysis. Gene-environment interaction was evaluated by a multiplieative model with combined OR. All data were analyzed using SAS version 8.2 software. Results No significant difference in frequency of the TNF-α-308 genotype was found between CWP complicated with pulmonary TB and non-TB controls （2,2=5.44, P=-0.07）. But difference in frequency of the TNF-α-308 A allele was identified between them （2,2-5.14, P=0.02）. No significant difference in frequencies of the TNF-α-238 genotype and allele （P=0.23 and P=0.09, respectively） was found between cases and controls either, with combined （GG and AA） OR of 3.96 （95% confidence interval of 1.30-12.09） at the -308 locus of the TNF-α gene, as compared to combination of the TNF-α-238 GG and TNF-α-308 GG genotypes. Multivariate-adjusted odds ratio of the TNF-α-238 GG and TNF-α-308 GA genotypes was 1.98 （95% CI of 1.06-3.71） for risk for pulmonary TB in patients with CWP. There was a synergic interaction between the TNF-a-308 GG genotype and body mass index （OR=4.92）, as well as an interaction between the TNF-α-308 GG genotype and history of BCG immunization or history of TB exposure. And, the interaction of the TNF-α-238 GG genotype and history of BCG immunization or TB exposure with risk for pulmonary TB in them was also indicated. Conclusions TNF-α-308 A allele is associated with an elevated risk for pulmonary TB, whereas TNF-α-238 A allele was otherwise.

TNF-α and IL-1RA Polymorphisms and Silicosis Susceptibility in Chinese Workers Exposed to Silica Particles:A Case-Control Study

Abstract Objective To assess the association of TNF-α and IL-1RA SNPs with the risk of silicosis in Chinese workers exposed to silica particles. Methods Case-control study design was used to enroll 68 silicotic patients induced by silica particles and 68 healthy workers matched for length of silica particle exposure as controls. Both cases and controls were from the same company in southwest China, and each of them was requested to complete a questionnaire. Blood samples were drawn for genomic DNA extraction from each participant. The genotyping of TNF-α （-238 and -308） and IL-1RA （＋2018） was performed using polymerase chain reaction-based restriction fragment length polymorphism （PCR-RFLP） and SYBR green-based quantitative polymerase chain reaction {qPCR）, respectively. Unconditional logistic regression model was used to estimate odds ratios （ORs） and their 95% confidential intervals （Cl） for SNPs. Results No significant differences were found between cases and controls in particles exposure length, body mass index （BMI）, and status of smoking and alcohol consumption except for age （P=O.O01） and blood type （P=0.042）. The frequencies of TNF-c（（-238） and IL-1RA （＋2018） genotypes in cases were significantly different from those in controls, （P=O.O01 and P=0.O02, respectively）, while a borderline significant difference was found in the frequencies of TNF-α（-308） between cases and controls （P=0.063）. The variants of three SNPs increased the risk of silicosis in the Chinese workers exposed to silica particles. The adjusted ORs of TNFα（-308）, TNF-α（-238） and IL-1RA （＋2018） were 2.8 （95% Ch 2.1-7.5）, 20.9 （95% Ch 2.8-236.4） and 4.0 （95% CI： 2.6-10.2）, respectively. Conclusion It is suggested that cytokine polymorphisms of TNF-ct （-238, -308） and IL-1RA （＋2018） are associated with the risk of silicosis in the Chinese workers exposed to silica particles. Further independent studies on the interaction between SNPs and exposure to silica particles with a larger sample size are therefore warranted.

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.

The Association between Polymorphism of TNF-α Gene and Hypertensive Disorder Complicating Pregnancy

To study whether the development of hypertensive disorder complicating pregnancy is associated with --308G→A, -850C→T mutation at promoter of TNF-α gene, the --308G→A, --850C→T polymorphism was examined in patients and healthy pregnant women by PCR-RFLP technique. The frequencies of genotype and allele were compared between the two groups. The results showed that with-308G→A polymorphism distribution, the allele frequency of TNF2 and the frequency of the genotype TNF2/1 in the patient group was significantly higher in the patient group than in control group （P〈0.05）. A significant difference in genotype distribution of --850C→T polymorphism was observed between the two groups. The allele frequencies of T in patient group was higher in the control group as compared with the patient group. The frequencies of CT and TT genotypes were lower in the patient group. It is concluded that the TNF2 allele of -308 is associated with the occurrence of hypertensive disorder complicating pregnancy, while T allele of--850 may be the protective factor against the development of the disease. TNF2/1 CC may be susceptibility genotype of hypertensive disorder complicating pregnancy.

Effect of cytotoxic T-lymphocyte antigen-4,TNF-alpha polymorphisms on osteosarcoma: evidences from a meta-analysis

Objective： Previous studies have investigated the role of cytotoxic T-lymphocyte antigen-4 （CTLA-4） and tumor necrosis factor-alpha （TNF-a） in carcinogenesis of osteosarcoma, but their results were inconsistent. We aimed to clarify the associations between CTLA-4, TNF-a polymorphism and osteosarcoma risk by using meta-analysis. Methods： We searched relevant studies without language restriction in PubMed, EMbase, Cochrane Library, Google Scholar databases, Chinese National Knowledge Infrastructure （CNKI） and conference literature in humans published prior to March 2013. The strengths of the associations between genetic variants and osteosarcoma risk were estimated by odds ratio （OR） with 95% confidence interval （95% CI）. Results： A total of seven studies with 1,198 osteosarcoma patients and 1,493 controls were selected. Four studies were eligible for CTLA-4 （1,003 osteosarcoma and 1,162 controls）, and three studies for TNF-a （195 osteosarcoma and 331 controls）. Pooled results showed that rs231775 polymorphism of CTLA-4 was associated with osteosarcoma risk （GG vs. AA： OR=1.63, 95% CI=1.24-2.13; GG ＋ GA vs. AA： OR=1.56, 95% CI=1.21-2.01; AA ＋ GA vs. GG： OR=0.83, 95% CI=0.71-0.97; G vs. A： OR=1.21, 95% CI=1.08-1.36）. No significant heterogeneity was observed across the studies. No significant associations were found between rs5742909 polymorphism of CTLA-4 or rs1800629 polymorphism of TNF-a and osteosarcoma risk. Conclusions： These results suggest that the rs231775 polymorphism of CTLA-4 may play an important role in carcinogenesis of osteosarcoma.

Association between TNF-308G/A polymorphism and susceptibility to pulmonary tuberculosis in the Lur population of Iran

Objective:To investigate whether tumor necrosis factor-α(TNFα)-238G/A and-308G/A polymorphisms are associated with susceptibility to pulmonary tuberculosis(TB) in the Lur ethnic population of Iran.Methods:TNF polymorphisms genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism method in 100 pulmonary TB patients and 100 healthy controls from the Lur population.Results:The allelic and genotypic frequencies of TNFα-238G/A polymorphism were not significantly different between the pulmonary TB patients and the healthy controls.However,the TNFα-308G/A polymorphism showed a significantly higher frequency of genotype GG in TB subjects compared to healthy controls(94% in the patients vs.62% in the controls,P = 0.0001,odds ratio = 0.104,confidence interval = 0.028-0.382).Moreover,in the TNFα-308G/A polymorphism,a significantly higher frequency of G allele was measured in the patient group compared with the control group(97%in the patient group vs.81% in the control group,P=0.0001,odds ratio = 0.132,confidence interval = 0.038-0.462).Conclusions:Our findings suggest that TNFα-308G/A polymorphism may increase the susceptibility to pulmonary TB in the Lur population of Iran.Despite TNFα polymorphisms and susceptibility to pulmonary TB,we suggest that more studies with larger sample size are needed in the future.Increasing our understanding of susceptibility risk factors may help to improve current preventive measures and treatment for TB.

Association of miR-146 rs2910164,miR-196a rs11614913,miR-221 rs113054794 and miR-224 rs188519172 polymorphisms with anti-TNF treatment response in a Greek population with Crohn's disease

AIM To investigate the correlation between rs2910164, rs11 614913, rs113054794, and rs188519172 polymorphisms and response to anti-TNF treatment in patients with Crohn's disease(CD). METHODS One hundred seven patients with CD based on standardclinical, endoscopic, radiological, and pathological criteria were included in the study. They all received infliximab or adalimumab intravenously or subcutaneously at standard induction doses as per international guidelines. Clinical and biochemical response was assessed using the HarveyBradshaw index and CRP levels respectively. Endoscopic response was evaluated by ileocolonoscopy at week 12-20 of therapy. The changes in endoscopic appearance compared to baseline were classified into four categories, and patients were classified as responders and nonresponders. Whole peripheral blood was extracted and genotyping was performed by PCR.RESULTS One hundred and seven patients were included in the study. Seventy two(67.3%) patients were classified as complete responders, 22(20.5%) as partial while 13(12.1%) were primary non-responders. No correlation was detected between response to anti-TNF agents and patients' characteristics such as gender, age and disease duration while clinical and biochemical indexes used were associated with endoscopic response. Concerning prevalence of rs2910164, rs11614913, and rs188519172 polymorphisms of miR-146, miR-196a and miR-224 respectively no statistically important difference was found between complete, partial, and non-responders to antiTNF treatment. Actually CC genotype of rs2910164 was not detected in any patient. Regarding rs113054794 of miR-221, normal CC genotype was the only one detected in all studied patients, suggesting this polymorphism is highly rare in the studied population.CONCLUSION No correlation is detected between studied polymorphisms and patients' response to anti-TNF treatment. Polymorphism rs113054794 is not detected in our population.

The association of TNF-308(G/A) gene polymorphisms and hepatocellular carcinoma risk: a meta-analysis

Objeotive： Many studies have examined the association between the TNF-308 G/A polymorphism gene polymorphisms and hepatocellular carcinoma risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, a me：a-analysis was performed. Methods： The PubMed and CNKI （China National Knowledge Infrastructure） database was searched for case-control studies. Odds ratios （OR） with 95% CIs were used to determine the strength of association between the TNF-308 G/A polymorphisms and HCC risk. The pooled ORs for the risk associated with the TNF-308 G/A genotype, the A carriers （A/G ＋ A/A） vs. the wild-type homozygntes （G/G）, A/A vs. G/G were calculated, respectively. Subgroup analyses were done by ethnicity and smoking status. Heterogeneity assumptions were assessed by chi-square-based Q-test. Results： Ultimately, 21 studies, comprising 2,923 hepatocellular carcinoma cases and 4,323 controls were included. Overall, the A carriers （G/A ＋ A/A） vs. the wild-type homozygotes （G/G）, the pooled OR was 1.05 （95% CI, 0.93-1.19; P=0.000 for heterogeneity）, for A/A vs. G/G the pooled OR was 1.07 （95% CI, 0.95-1.21; P=0.007 for heterogeneity）. In the stratified analysis by erhnicity, the significantly risks were found among non-Asians. However, for Asians, significantly risks were not found. Conclusions： The TNF-308 G/A polymorphisms are not associated with hepatoceUular carcinoma risk among Asians, but for non-Asians.

Influence of polymorphisms in VEGF, ACE, TNF and GST genes on the susceptibility to retinopathy of prematurity among Chinese infants

AIM： To investigate common polymorphisms in VEGF, ACE, TNF and GST genes with retinopathy of prematurity（ROP） risk among Chinese infants. METHODS： Nine polymorphisms in the above genes were genotyped on 724 advanced cases of ROP and 878 prematurely-born infants of low birth weight who were without any ophthalmologic disease. The frequencies of the polymorphisms were compared between cases and controls to identify the association present, if any. RESULTS： Of the nine polymorphisms, only two showed significant associations： ACE insertion deletion（ID） polymorphism（P=0.031） and TNF-308 G/A polymorphism（P〈0.001）. The former was associated with a reduced ROP risk [ID genotype, adjusted OR（aOR）： 0.603, 95%CI： 0.427-0.893, P=0.034; DD genotype, aOR： 0.468, 95%CI： 0.229-0.626, P=0.002], while the latter showed an increased risk（GA genotype, aOR： 1.956, 95%CI： 1.396-2.465, P〈0.001; AA genotype, aOR： 2.809, 95%CI： 1.802-4.484, P〈0.001）. The association was also noted at the allele level（ACE D allele a OR： 0.698, 95%CI： 0.294-0.883, P〈0.001; TNF-308A allele a OR： 1.776, 95%CI： 1.446-2.561, P〈0.001）. CONCLUSION： The ACE ID polymorphism can protect against ROP development while the TNF-308G/A can increase the risk of the disease among Chinese infants.

TNF-a-308 polymorphism and risk of digestive system cancers:A meta-analysis

AIM:To evaluate the association between the tumour necrosis factor alpha-308(TNF-a-308)gene polymorphism and the risk of digestive system cancers.METHODS:All eligible case-control studies published up to December 2012 were identified by searching PubMed,Web of Science,Embase and China National Knowledge Internet without language restrictions.The risk of digestive system cancers associated with the TNF-a-308 polymorphism was estimated for each study using odds ratio(OR)together with its 95%CI,respectively.Cochrane Collaboration RevMan 5.1 was used to perform the analysis.Aχ2-test-based Q statistic test and an I2test were performed to assess the betweenstudy heterogeneity.When the Q test was significant(P<0.05)or I2>50%,the random effects model was used,otherwise the fixed effects model was used.RESULTS:Fifty-eight studies from fifty-five publications with a total of 9986 cancer patients and 15511 healthy controls were included.Overall,a significant association was found between the TNF-a-308 polymorphism and the risk of digestive system cancers[dominant model:OR=1.23,95%CI:1.09-1.39,(G/A)vs(G/G):OR=1.15,95%CI:1.02-1.28,(A/A)vs(G/G):OR=1.44,95%CI:1.19-1.73,recessive model:OR=1.38,95%CI:1.15-1.66].Furthermore,when the analysis was stratified by ethnicity,similar results were observed in both the Asian and Caucasian populations,except for the dominant model and heterozygote comparisons in the Asian population[dominant model:OR=1.24,95%CI:0.99-1.56,(G/A)vs(G/G):OR=1.09,95%CI:0.96-1.24].When the cancer type subgroups were examined,similar results were detected in gastric and hepatocellular carcinomas;however,no significant association was observed among other digestive system cancers.CONCLUSION:The TNF-a-308 gene polymorphism may be significantly associated with the risk of gastric and hepatocellular carcinomas,but not colorectal,pancreatic,or oesophageal cancer,in the Asian population.

TNF-α gene polymorphisms: association with age-related macular degeneration in Russian population

AIM: To study polymorphisms in promotor regions of tumor necrosis factor(TNF)-α TNF-863 A/C(rs1800630), TNF-308 A/G(rs1800629), and TNF-238 A/G(rs361525) in patients with age-related macular degeneration(AMD) and associations of complex TNF-α genotypes with AMD. METHODS: One hundred and two patients(82 women, 20 men; mean age 64.2±1.2 y) with AMD and 100 healthy age-and sex-matched controls(82 women, 18 men; 60±1.4 y) were included in the study. All subjects were Caucasian, all subjects and their parents were inhabitants of Russia. Genomic DNA was obtained from EDTA-preserved blood using the standard phenol-chloroform method. Polymorphisms were detected by polymerase chain reaction followed by the restriction fragment length polymorphism method. The following TNF-α genotypes were studied: TNF-α-238 AA, GA, GG, TNF-α-308 AA, GA, GG, TNF-α-863 AA, CA, CC. RESULTS: Differences in TNF-α-863 and TNF-α-238 genotypes frequencies in patients with AMD and healthy controls were not found. The distribution of TNF-α-308 AA and TNF-α-308 GA genotypes was significantly different between the studied group and the controls [odds ratios(OR) =0.22, P=0.0287 and OR=2.91, P=0.0063, respectively]. TNF-863 CC/TNF-308 GA and TNF-308 GA/TNF-238 GG genotypes were associated with the increased risk of AMD(OR=2.48, P=0.0332 and OR=2.51, P=0.0187, respectively). Five genotypes combinations appeared to be protective. CONCLUSION: In the present study, single nucleotide polymorphisms and complex polymorphisms of one of the key inflammatory cytokines TNF-α, and a number of significant associations of these polymorphisms with AMD in Russian population have been shown. Complexanalysis of genotypes could be important in AMD risk factors detection and studying pathogenesis.

Association of UCP3,APN,and TNF-α Gene Polymorphisms with Type 2 Diabetes in a Population of Northern Chinese Han Patients

We observed the polymorphism distribution and coaction of uncoupling protein 3（UCP3）-55C/T,adiponectin（APN）＋45T/G and tumor necrosis factor（TNF）-α-308G/A on the onset and development of T2DM in a Northern Chinese Han population of 213[100 type 2 diabete（T2DM） patients and 113 health control subjects] by polymerase chain reaction-restriction fragment length polymorphisum（PCR-RFLP） method.Results demonstrate the polymorphism of UCP3-55C/T,APN＋45T/G,and TNF-α-308G/A related to T2DM onset and developement.And the individuals carrying UCP3-55T,APN＋45G and TNF-α-308A allele had higher T2DM risk.Those results are the first report to evaluate the association of the coaction of UCP3,APN,TNF-α genes polymorphism on T2DM risk and the susceptibility of T2DM in the Northern Chinese Han population.

Influences of polymorphism of packed particles on bulk characterizations in fluidization realm

The characterization of a particle ensemble(rather than a single particle) is of paramount significance to various particle technologies and has long been a fundamental subject in the fluidization realm. However, many of such bulk characterizations as loosely-packed density(ρbl), minimum fluidization velocity(Umf), sphericity(φ), discharge rate through orifice(q), angle of repose(β), and segregation index(S),were found to be poorly reproducible, making the reported results seldom comparable. Since these bulk characterizations started from the packed state of particles, such poor reproducibility was ascribed to the polymorphism of packed particles in this work. We observed that in the fluidized bed, the settled/packed state of particles varied monotonously with the settling rate(a) from complete fluidization to zero. This phenomenon confirmed the polymorphic characteristic of packed particles and further enabled us to systematically disclose/clarify its influences on the aforementioned bulk characterizations. Such influences could be comprehensively and intuitively reflected by the impacts induced by a. With the decrease of a, ρbl, φ and q first increased, then decreased, and finally leveled off while Umfand β showed an opposite trend. On the other hand, S first increased and then remained invariant. As per these findings and definitions of these bulk characterizations, benchmarks were indicated to unify the selection of settled state among future scholars and further make their outcomes become fairly comparable. Additionally, most packed states of the particle ensemble were proved to be metastable with their formation and behavior being identical to those of the amorphous state.

Relationship between the rs2241766 ADIPOQ Polymorphism in a Black African Population and the Occurrence of Type 2 Diabetes

Background: Type 2 diabetes mellitus (T2DM) is a metabolic disease, characterized by chronic hyperglycemia. This pathology is linked to various genes whose interaction with the environment promotes its development. The aim of this work was to determine the relationship between the rs2241766 (T/G) polymorphism of the ADIPOQ gene with type 2 diabetes in the black population. Material and Methods: This work was a case-control study, involving type 2 diabetics subjects (n = 94) and controls (n = 82). The study took place from September 2022 to September 2023. Patients were recruited in the Endocrinology Department of the Libreville University Hospital Center. Analysis was performed in the Biochemistry laboratory of the University of Health Sciences in Libreville and at the Research Institute of Health Sciences of Bobodioulasso. Genomic DNA was extracted using the protocol Qiagen kit and the PCR-RFLP method was used to determine the rs2241766 (T/G) polymorphism of the ADIPOQ gene. Results: Only 2 genotypes were found in this population, the TT genotype and the GT genotype. The proportions were not different between the two groups (p = 0.1095) neither the distribution of G and T alleles (p = 0.1095). On the other hand, the HDL hypocholesterolemia was frequent in subjects with the GT genotype compared to TT heterozygous (51.1% vs 48.9%, p = 0.0280;OR = 0.55 [0.30 - 1.01]). Conclusion: There was no association between the rs2241766 (T/G) variant of the ADIPOQ gene and the occurrence of type 2 diabetes in this population. On the other hand, a relationship between HDL hypocholesterolemia and the GT genotype has been established.

Single nucleotide polymorphism within chromosome 8q24 is associated with prostate cancer development in Saudi Arabia

Objective: Genome-wide association studies have demonstrated that single nucleotide polymorphisms (SNPs) are important risk factors for the development of prostate cancer (PCa). Preliminary studies have suggested that the incidence of PCa in Saudi males is low but is probably familial or genetically related.Methods: To identify any possible association of SNP with PCa development in Saudi patients, we investigated a group of SNPs in Saudi PCa patients (n=85) and compared the outcomes to healthy normal controls (n=115) and nodular hyperplasia patients (n=120). DNA was extracted from paraffin-embedded formalin fixed tissue or whole blood from both patients’ groups and healthy control group. A total of thirteen SNPs were genotyped using TaqMan® minor groove binder polymerase chain reaction assay.Results: The rs16901979A, s629242T and rs1447295A alleles were found at significantly higher frequency in PCa patients than controls (p< 0.05). The rs16901979 CA genotype was found at significantly greater frequency in PCa patients than in healthy controls (43% vs. 14%, odds ratio=4.6, p=0.0001) and benign hyperplasia group (43% vs. 25%, odds ratio=2.2, p=0.009).Conclusion: Our study has highlighted the association of rs16901979 SNP with PCa in Saudi males. Such findings have important implications in the PCa diagnosis and in screening unaffected family members of Saudi patients.

Nucleotide excision repair gene polymorphisms and hepatoblastoma susceptibility in Eastern Chinese children:A five-center case-control study

Objective:Nucleotide excision repair(NER)plays a vital role in maintaining genome stability,and the effect of NER gene polymorphisms on hepatoblastoma susceptibility is still under investigation.This study aimed to evaluate the relationship between NER gene polymorphisms and the risk of hepatoblastoma in Eastern Chinese Han children.Methods:In this five-center case-control study,we enrolled 966 subjects from East China(193 hepatoblastoma patients and 773 healthy controls).The TaqMan method was used to genotype 19 single nucleotide polymorphisms(SNPs)in NER pathway genes,including ERCC1,XPA,XPC,XPD,XPF,and XPG.Then,multivariate logistic regression analysis was performed,and odds ratios(ORs)and 95%confidence intervals(95%CIs)were utilized to assess the strength of associations.Results:Three SNPs were related to hepatoblastoma risk.XPC rs2229090 and XPD rs3810366 significantly contributed to hepatoblastoma risk according to the dominant model(adjusted OR=1.49,95%CI=1.07−2.08,P=0.019;adjusted OR=1.66,95%CI=1.12−2.45,P=0.012,respectively).However,XPD rs238406 conferred a significantly decreased risk of hepatoblastoma under the dominant model(adjusted OR=0.68,95%CI=0.49−0.95;P=0.024).Stratified analysis demonstrated that these significant associations were more prominent in certain subgroups.Moreover,there was evidence of functional implications of these significant SNPs suggested by online expression quantitative trait loci(eQTLs)and splicing quantitative trait loci(sQTLs)analysis.Conclusions:In summary,NER pathway gene polymorphisms(XPC rs2229090,XPD rs3810366,and XPD rs238406)are significantly associated with hepatoblastoma risk,and further research is required to verify these findings.

Relationship between Single Nucleotide Polymorphism in TNF-α Gene Promoter Region and Inhibitory Effects of Triptolide on TNF-α Production in Peripheral Blood Mononuclear Cells of Healthy Humans

The relationship between tumour necrosis lactose （TNF-α） gene polymorphism and inhibitory effects of triptolide on TNF-α production from peripheral blood mononuclear cells （PBMC） of healthy humans was investigated. Genomic DNA from 41 healthy people was typed for TNF-α- 308 polymorphism by allele-specific polymorphism chain reaction （AS-PCR）. The TNF-α concentration in the supernatant was measured by ELISA. The results showed that the production of TNF-α from TNF-α -308 non-G/G genotype PBMC was higher than that from TNF-α-308 G/G genotype PBMC after stimulated by LPS. Triptolide could lower the production of TNF-α from G/ G genotype PBMC, but had no effect on the level of TNF-α from non-G/G genotype PBMC. It was concluded that TNF-α gene polymorphism was related to the TNF-α production from triptolide-inhibited PBMC culture in healthy humans.

PNPLA3 and TNF-α G238A Genetic Polymorphisms in Egyptian Patients with Different Grades of Severity of NAFLD

Introduction: There is growing evidence that genetic and environmental factors play an important role in the development and progression of non-alcoholic fatty liver disease (NAFLD). We investigated the association of single nucleotide polymorphism (SNP) rs738409 in PNPLA3 gene and TNF-α G238A polymorphism with the development and severity of NAFLD in an overweight and obese Egyptian population. Material and Methods: 100 overweight and obese patients with NAFLD and 30 control subjects were enrolled. All NAFLD patients underwent a confirmatory biopsy. Laboratory investigations included fasting plasma glucose, kidney and liver function tests, liver enzymes, lipid profile and hepatitis markers. Abdominal ultrasound was performed and all subjects were genotyped for (rs738409) PNPLA3 and (rs361525) TNF-α gene polymorphisms using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Results: The homozygous GG genotype of the PNPLA3 was most frequent among patients with NASH (26%) as compared to borderline NASH (20.5%) and simple steatosis (20%). Higher serum levels of transaminases were observed in NAFLD patients and controls who were carriers of the G allele of rs738409, but this was not statistically significant. Regarding the TNF-α G238A SNP;the frequency of the A allele was significantly higher in NAFLD patients (20%) compared to controls (5%) (p value = 0.006). The highest TNF G allele frequency was observed in the NASH group (88%) and this was statistically significant (p value = 0.009). Conclusion: Our study confirmed the association of the PNPLA3 (rs738409) and TNF-α promoter region G238A polymorphisms with susceptibility to NAFLD and its progression.

Toll-like receptors 2 polymorphism is associated with psoriasis: A case-control study in the northern Chinese population

Background:Psoriasis is a disease caused by genetics and immune system dysfunction,affecting the skin and joints.Toll-like receptors(TLRs)play an important role in triggering the innate immune response and controlling adaptive immunity.The role of TLR2 in the progression of psoriasis is not well understood.Methods:A case-control study was conducted on a northern Chinese Han population,consisting of psoriasis patients and healthy control subjects.Genotyping was performed using the tetra-primer amplification refractory mutation system-polymerase chain reaction(ARMS-PCR),and allele and genotype frequencies of four SNPs in TLR2 were analyzed in 270 psoriasis patients and 246 healthy controls.Results:Four TLR2 SNPs(rs11938228,rs4696480,rs3804099,rs5743699)were genotyped and found to be in linkage disequilibrium.The genotype distributions of rs11938228 and rs4696480 in two groups were in Hardy-Weinberg equilibrium and statistically significant except for the overdominance model.The haplotypes ATTC and ATCC were found to be protective against psoriasis.Conclusion:Our study found a correlation between TLR2 genetic variations and the likelihood of psoriasis in northern China.

Evaluation of angiotensin converting enzyme insertion/deletion, alpha adducin (ADD1) G460W, and IL-10 gene polymorphisms, and determination of prognostic effects in idiopathic sudden sensorineural hearing loss

Objective:The aim of this study was to examine angiotensin converting enzyme(ACE)insertion/deletion,alpha adducin,and interleukin-10(IL-10)gene polymorphisms(GPs)in terms of both idiopathic sudden sensorineural hearing loss(ISSNHL)risk and their potential prognostic effects.Methods:The study group consisted of 70 patients and the control group consisted of 50 patients.Venous blood samples were analyzed for relevant GPs via kompetitive allele-specific polymerase chain reaction.Age,sex,affected side,tinnitus,and vertiginous symptom status,number of days between symptom onset and hospital admission,pure tone audiometry results at admission and after treatment were included in the study.Data were compared statistically.Results:The D allele of ACE insertion/deletion GP was significantly more frequent in patients with ISSNHL than in the control group(p=0.032).II genotype was associated with a reduced risk of ISSNHL(p=0.036).The amount of hearing loss was significantly higher in patients with the TT genotype(p=0.027)and T allele of the IL-10 GP(p=0.035)than in the patients without this allele.Severe hearing loss was a poor prognostic factor(p=0.008).Conclusions:The D allele of ACE insertion/deletion GP may be involved in the ISSNHL etiology.Due to the association of this allele with occlusive vascular pathologies,ischemia is believed to be a common pathway in the etiopathogenesis of ISSNHL.