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。

Glutamate decarboxylase 1 gene polymorphisms are associated with respiratory symptoms in panic disorder

BACKGROUND Genetic factors play an important role in the pathogenesis of panic disorder(PD).However,the effect of genetic variants on PD remains controversial.AIM To evaluate the associations between glutamate decarboxylase 1(GAD1)gene polymorphisms and PD risk and assess the effect of GAD1 gene polymorphisms on the severity of clinical symptoms in PD.METHODS We recruited 230 PD patients and 224 healthy controls in this study.All participants were assessed for anxiety and panic symptom severity using the Hamilton Anxiety Rating Scale(HAM-A)and Panic Disorder Severity Scale(PDSS).GAD1 gene polymorphisms(rs1978340 and rs3749034)were genotyped and assessed for allele frequencies.RESULTS There were no significant differences between cases and controls in the genotype distributions or allele frequencies of GAD1(rs1978340 and rs3749034).In addition,the effect of GAD1(rs1978340 and rs3749034)on PD severity was not significant.However,regarding respiratory symptoms,patients with the GAD1 rs1978340 A/A genotype had significantly higher scores than those with the A/G or G/G genotype.CONCLUSION Here,we showed that the A/A genotype of GAD1 rs1978340 was associated with increased severity of respiratory symptoms in patients with PD.

Cytokine and apoptosis gene polymorphisms influence the outcome of hepatitis C virus infection

BACKGROUND:Hepatitis C virus (HCV) infection is thought to be chronic and the factors leading to viral clearance or persistence are poorly understood.This study was undertaken to investigate the possibility of a significant relationship between the spontaneous clearance or the persistence of hepatitis C virus (HCV) infection and cytokine and apoptosis gene polymorphisms in Tunisian patients on hemodialysis.METHODS:Polymorphisms of the genes IL-1 (-889 IL-1α,-511 and +3954 IL-1β,IL-1Ra),IL-18 (-137 and-607),IL-12 (-1188) and Apo1/Fas (-670) were determined by PCR-RFLP,PCR-SSP and PCR-VNTR in 100 healthy blood donors and 100 patients infected with HCV and undergoing hemodialysis.The patients were classified into two groups:G1 consisted of 76 active chronic hepatitis patients (positive for HCV RNA) and G2 consisted of 24 hemodialysed patients who spontaneously eliminated the virus (negative for HCV RNA).RESULTS:The frequency of genotype association [-137GC/-607CA] IL-18 was higher in G2 (41.7%) than in G1 (15.8%) (P=0.008;OR=0.26;95% CI,0.10-0.73).We also found a higher frequency of the AA genotype of the Apo1/Fas gene in G2 (41.6%) than in G1 (17.5%) (P=0.026;OR=3.49;95% CI,1.13-10.69).Adjustment for known covariate factors (age,gender and genotype) confirmed these univariate findings and revealed that the genotype association GC-CA of the (-137 and-607) IL-18 gene and the AA genotype of the Apo1/Fas gene were associated with the clearance of HCV (P=0.041 and 0.017,respectively).CONCLUSION:The two genotypes GC-CA of the (-137 and-607) IL-18 polymorphism and the AA genotype of the Apo1/Fas gene influence the outcome of HCV infection in Tunisian patients on hemodialysis.

Inflammatory cytokine gene polymorphisms increase the risk of atrophic gastritis and intestinal metaplasia

AIM: To investigate the effects of interleukin-8 (IL-8 ), macrophage migration inhibitory factor (MIF ) gene polymorphisms, Helicobacter pylori (H. pylori ) infection, on the risk of developing severe chronic atrophic gastritis (SCAG) and intestinal metaplasia (IM). METHODS: A total of 372 cases were selected from a cohort study in Linqu County, a high risk area for gastric cancer (GC) in northern China. To obtain a sufficient group size, patients with normal or superficial gastritis were included. Based on an average follow-up period of 56 mo, the 372 cases were divided into no progres-sion group (no histological progression from normal or superficial gastritis, n = 137), group Ⅰ (progressed from normal or superficial gastritis to SCAG, n = 134) and group Ⅱ (progressed from normal or superficial gastritis to IM, n = 101). IL-8 , MIF gene polymorphisms were detected by polymerase chain reaction-based denaturing high-performance liquid chromatography analysis and DNA sequencing. RESULTS: An increased risk of SCAG was found in subjects with IL-8-251 AA genotype [odds ratio (OR) = 2.62, 95% CI: 1.23-5.72] or IL-8-251 A allele carriers (AA + AT) (OR = 1.81, 95% CI: 1.06-3.09). An elevated risk of IM was found in subjects with IL-8-251 AT genotype (OR = 2.27, 95% CI: 1.25-4.14) or IL-8-251 A allele carriers (OR = 2.07, 95% CI: 1.16-3.69). An increased risk of SCAG was found in subjects with MIF-173 GC genotype (OR = 2.36, 95% CI: 1.38-4.02) or MIF-173 C allele carriers (GC + CC) (OR = 2.07, 95% CI: 1.21-3.55). An elevated risk of IM was found in subjects with MIF-173 CC genotype (OR = 2.27, 95% CI: 1.16-4.46) or MIF-173 C allele carriers (OR = 3.84, 95% CI: 1.58-9.34). The risk of SCAG and IM was more evident in subjects carrying IL-8-251 A allele (OR = 6.70, 95% CI: 1.29-9.78) or MIF-173 C allele (OR = 6.54, 95% CI: 2.97-14.20) and positive for H. pylori infection. CONCLUSION: IL-8-251 and MIF-173 gene polymorphisms are significantly associated with the risk of SCAG and IM in a population with a high risk of GC in Linqu County, Shandong Province, China.

Correlating interleukin-10 promoter gene polymorphisms with human cerebral infarction onset

Evidence suggests that interleukin-10（IL-10） deficiency exacerbates inflammation and worsens the outcome of brain ischemia. In view of the critical role of the single nucleotide polymorphic sites-1082（A/G） and-819（C/T） in the promoter region of the IL-10 gene, we hypothesized that they are associated with cerebral infarction morbidity in the Chinese Han population. We genotyped these allelic gene polymorphisms by amplification refractory mutation system-polymerase chain reaction methods in 181 patients with cerebral infarction（cerebral infarction group） and 115 healthy subjects（control group）. We identified significant differences in genotype distribution and allele frequency of the IL-10-1082 A/G allele between cerebral infarction and control groups（χ2 = 6.643, P = 0.010）. The IL-10-1082 A allele frequency was significantly higher in the cerebral infarction group（92.3%） than in the control group（86.1%）（P = 0.015）. Moreover, cerebral infarction risk of the AA genotype was 2-fold higher than with the AG genotype（OR = 2.031, 95%CI： 1.134-3.637）. In addition, AA genotype together with hypertension was the independent risk factor of cerebral infarction（OR = 2.073, 95%CI： 1.278-3.364）. No statistical difference in genotype distribution or allele frequency of IL-10-819 C/T was found between cerebral infarction and control groups（P 〉 0.05）. These findings suggest that the IL-10-1082 A/G gene polymorphism is involved in cerebral infarction, and increased A allele frequency is closely associated with occurrence of cerebral infarction.

Association between ADIPOQ gene polymorphisms and the risk of new-onset diabetes mellitus after liver transplantation

BACKGROUND:New-onset diabetes after transplantation(NODAT) has become one of the major factors that affect the overall survival and long-term life quality in liver transplantation(LT) recipients. Previous studies found that the serum adiponectin concentration of diabetic patients is significantly lower than that of healthy subjects. Adiponectin regulates the blood glucose level by increasing body sensitivity to insulin through various mechanisms. In this study, we aimed to investigate the impact of diabetes related gene polymorphisms on the development of NODAT in liver recipients.METHODS:A total of 256 LT patients in a single-center were selected retrospectively for the study. Genomic DNA was extracted from explanted liver tissues, and tested for twelve diabetes mellitus associated single nucleotide polymorphisms by Sequenom Mass ARRAY. Modified clinical models in predicting NODAT were established and evaluated.RESULTS:The GG genotype of ADIPOQ rs1501299 gene polymorphism was significantly more frequent in NODAT than non-NODAT LT patients(56% vs 39%, P=0.014). Dominant model(GG vs GT+TT, P=0.030) and recessive model(GT+GG vs TT, P=0.005) also confirmed the genotype distribution difference between NODAT and non-NODAT groups. Age(OR=1.048, P=0.004), BMI(OR=1.107, P=0.041), and blood tacrolimus level at 1-month LT(OR=1.170, P=0.003) were clinical independent risk factors of NODAT. Furthermore, rs1501299 could improve the ability of clinical model in predicting NODAT(AUROC=0.743, P<0.001).CONCLUSION:ADIPOQ rs1501299 gene polymorphism is associated with an increased risk of NODAT, which should be added to the clinical models in predicting the occurrence of NODAT in LT recipients.

Serotonin type 3 receptor subunit gene polymorphisms associated with psychosomatic symptoms in irritable bowel syndrome:A multicenter retrospective study

BACKGROUND Single-nucleotide polymorphisms(SNPs)of the serotonin type 3 receptor subunit(HTR3)genes have been associated with psychosomatic symptoms,but it is not clear whether these associations exist in irritable bowel syndrome(IBS).AIM To assess the association of HTR3 polymorphisms with depressive,anxiety,and somatization symptoms in individuals with IBS.METHODS In this retrospective study,623 participants with IBS were recruited from five specialty centers in Germany,Sweden,the United States,the United Kingdom,and Ireland.Depressive,anxiety,and somatization symptoms and sociodemographic characteristics were collected.Four functional SNPs—HTR3A c.-42C>T,HTR3B c.386A>C,HTR3C c.489C>A,and HTR3E c.*76G>A—were genotyped and analyzed using the dominant and recessive models.We also performed separate analyses for sex and IBS subtypes.SNP scores were calculated as the number of minor alleles of the SNPs above.The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays.RESULTS Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model(F_(depressive)=7.475,P_(depressive)=0.006;F_(anxiety)=6.535,P_(anxiety)=0.011).A higher SNP score(range 0-6)was linked to a worsened depressive symptoms score(F=7.710,P-linear trend=0.006)in IBS.The potential relevance of the HTR3C SNP was corroborated,showing changes in the expression level of 5-HT3AC variant receptors.CONCLUSION We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS.The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.

Interactions of the apolipoprotein A5 gene polymorphisms and alcohol consumption on serum lipid levels

Objectives Apolipoprotein(Apo) A5 gene poly-morphisms and alcohol consumption have been associated with increased serum triglyceride(TG) levels,but little is known about their interactions on serum lipid levels.The present study was undertaken polymorphismsand alcohol consumption on serum lipid levels.Methods A total of 516 unrelated nondrinkers and 514 drinkers aged 15 -89 were randomly selected from our previous stratified randomized cluster samples.Genotyping of the ApoA5was performed by polymerase chain reaction and restriction fragment length polymorphism,and then confirmed by direct sequencing.Interactions of the ApoA5alcohol consumption were assessed by using a cross-product term between genotypes and the aforementioned factor.Results The levels of total cholesterol (TC),TG,high-density lipoprotein cholesterol(HDL-C), ApoA1 and ApoB were higher in drinkers than in nondrinkers (P【0.05-0.001).The genotypic and allelic frequencies of the three single nucleotide polymorphisms(SNPs) were not different between the two groups.The levels of TG in non-drinkers, and TC,TG,low-density lipoprotein cholesterol (LDL-C)and ApoB in drinkers were different among the three -1131T】C genotypes(P【0.05-0.001).The -1131C allele carriers had higher serum TC,TG,LDL-C and ApoB levels than the allele noncarriers.The levels of TG,HDL-C and ApoB in nondrinkers,and TG and HDL-C in drinkers were different between the two c.553G】T genotypes(P【0.05-0.01).The C.553T allele carriers had higher serum TG and ApoB levels,and lower HDL-C levels than the allele noncarriers.Serum lipid levels in nondrinkers were not different among the three c.457G】A genotypes(P【0.05 for all), but the levels of HDL-C,LDL-C,ApoA1 and ApoB in drinkers were different between the GG and GA/AA geno-types (P【0.05-0.001).The C.457A allele carriers had lower serum HDL-C,LDL-C,ApoAl and ApoB levels than the allele noncarriers.We also observed four haplotypes:G-G-T, G-G-C,G-A-T,and T-G-C with frequencies ranging from 0.06 to 0.87,representing 100%of all haplotypes in the both populations.The ApoA5 haplotypes were significantly(P【0.05) associated at the global level with TC,TG,HDL-C, LDL-C,Apo1,and ApoB,even after correction for multiple testing with permutation test.In particular,carriers of haplo-type G-G-C had significantly higher TC,TG,LDL-C,ApoB than noncarriers,whereas carriers of haplotype C-A-T had significantly lower TC,LDL-C,ApoAl and ApoB,and higher HDL-C than noncarriers.Serum TC levels in nondrinkers were correlated with -1131T】C genotype and allele(P【0.05 for each),whereas serum TC,TG and LDL-C levels in drinkers were associated with -1131 T】C and C.553G】T genotypes,or c.457G】A alleles(P【0.05-0.001).Serum lipid parameters were also correlated with several environmental factors in the both groups.Conclusions The differences in serum lipid profiles between the drinkers and nondrinkers might partly result from different interactions of ApoA5 gene polymor phisms and alcohol consumption.genotypes and -1131T】C, c.553G】T and c.457G】A to detect the interactions of the ApoA5

Association ofALOX5,LTA4H and LTC4S gene polymorphisms with ischemic stroke risk in a cohort of Chinese in east China

BACKGROUND:Genetic variations of the 5-lipoxygenase activating protein and leukotriene A4 hydrolase genes that confer an increased risk of ischemic stroke have implicated the family of leukotrienes as potential mediators of ischemic stroke.This study aimed to explore the association of ALOX5,LTA4 H and LTC4 S gene polymorphisms with ischemic stroke risk in a cohort of Chinese in east China.METHODS:This case-control study consisted of 690 patients with ischemic stroke and 690 controls.Polymorphisms of ALOX5 rs2029253 A/G,LTA4 H rs6538697 T/C,and LTC4 S rs730012 A/C were genotyped by the polymerase chain reaction and restriction fragment length polymorphism(PCR-RFLP) analysis.The multivariate logistic regression model was used to exclude the effects of conventional risk factors on ischemic stroke.RESULTS:Carriers of C allele in rs730012 were more susceptible to ischemic stroke(OR:1.37;95%CI:1.08-1.73;P=0.009).The rs2029253 GG genotype showed a risk-reducing effect on ischemic stroke(OR:0.72;95%CI:0.55-0.93;P=0.013) while the rs6538697 CC genotype had an increased risk of ischemic stroke(OR:1.77;95%CI:1.09-2.89;P=0.022).The rs730012 variant was not associated with ischemic stroke risk after adjusting confounding factors(P>0.05).CONCLUSION:The present study suggested that gene polymorphisms in the leukotrienes pathway may exert influences,with independent genetic effects,on ischemic stroke susceptibility in a cohort of Chinese in east China.

DCDC2 gene polymorphisms are associated with developmental dyslexia in Chinese Uyghur children

Developmental dyslexia is a complex reading and writing disorder with strong genetic components. In previous genetic studies about dyslexia, a number of candidate genes have been identified. These include DCDC2, which has repeatedly been associated with developmental dyslexia in various European and American populations. However, data regarding this relationship are varied according to population. The Uyghur people of China represent a Eurasian population with an interesting genetic profile. Thus, this group may provide useful information about the association between DCDC2 gene polymorphisms and dyslexia. In the current study, we examined genetic data from 392 Uyghur children aged 8–12 years old from the Xinjiang Uyghur Autonomous Region of China. Participants included 196 children with dyslexia and 196 grade-, age-, and gender-matched controls. DNA was isolated from oral mucosal cell samples and fourteen single nucleotide polymorphisms（rs6456593, rs1419228, rs34647318, rs9467075, rs793862, rs9295619, rs807701, rs807724, rs2274305, rs7765678, rs4599626, rs6922023, rs3765502, and rs1087266） in DCDC2 were screened via the SNPscan method. We compared SNP frequencies in five models（Codominant, Dominant, Recessive, Heterozygote advantage, and Allele） between the two groups by means of the chi-squared test. A single-locus analysis indicated that, with regard to the allele frequency of these polymorphisms, three SNPs（rs807724, rs2274305, and rs4599626） were associated with dyslexia. rs9467075 and rs2274305 displayed significant associations with developmental dyslexia under the dominant model. rs6456593 and rs6922023 were significantly associated with developmental dyslexia under the dominant model and in the heterozygous genotype. Additionally, we discovered that the T-G-C-T of the four-marker haplotype（rs9295619-rs807701-rs807724-rs2274305） and the T-A of the two-marker haplotype（rs3765502-1087266） were significantly different between cases and controls. Thus, we conclude that DCDC2 gene polymorphisms are associated with developmental dyslexia in Chinese Uyghur children.

Susceptibility of spinal tuberculosis and its related gene polymorphisms

Spinal tuberculosis,as one of the most serious forms of extrapulmonary tuberculosis,is one of the primary causes of spinal deformity and paralysis in developing countries.It immensely affects people's quality of life with high incidences of deformity and disability.The onset of spinal tuberculosis is related to many factors such as gender,age,environment,habits and hereditary factor.As a genetic factor,gene polymorphism plays an important role in the occurrence and development of tuberculosis.This article reviews the research progress of the susceptibility of spinal tuberculosis and its related gene polymorphisms,in order to provide reference for early prevention and treatment of spinal tuberculosis.

Plasma Homocysteine and Gene Polymorphisms Associated with the Risk of Hyperlipidemia in Northern Chinese Subjects

Objective To examine the relationship between occurrence of hyperlipidemia, plasma homocysteine and polymorphisms of methylenetetra hydrofolate reductase （MTHFR） gene and methionine synthase （MS） gene. Methods A total of 192 hyperlipidemia patients were selected and divided into hypercholesterolemia group, hypertriglyceridemia group, and combined hyperlipidemia group. Another 208 normal individuals were selected as control. Total plasma homocysteine （tHcy） concentration was measured by high-performance liquid chromatography （HPLC）. Lipid profiles were measured for all subjects The polymorphisms of MTHFR gene C677T and MS gene A2756G were analyzed by PCR-RFLP. Results The tHcy concentration in the combined hyperlipidemia patients was significantly higher than that in the control （15.95μmol/L vs 13.43 μmol/L, P〈0.05）. The prevalence of hyperhomocysteinemia （HHcy） in the combined hyperlipidemia group was significantly higher than that in the control （42.2% vs 23.0%, P=0.015）, with the odds ratio （OR） of 3.339 （95%CI： 1.260-8.849）. The hyperlipidemia patients with HHcy had a higher concentration of total cholesterol （TC） than that in the normal tHcy patients （5.67±0.95 mmol/L vs 5.47±0.92 retool/L, P=0.034）. There was no significant difference in genotype or allele frequencies of MTHFR C677T between the hyperlipidemic and control groups. The hyperlipidemia patients with MTHFR CT/TT genotype had a higher concentration of triglyceride （TG） than those with CC genotype （2.24±1.75 mmol/L vs 1.87±0.95 mmol/L, P〈0.05）. Individuals with CT/TT genotype had a higher concentration of tHcy than those with 677CC genotype both in the hyperlipidemia group （12.61±1.24μmol/L vs 11.20±1.37 μmol/L, P〈0.05） and in the control group （14.04±1.48 μmol/L vs 12.61±1.24 μmol/L, P〈0.05）. The percentage of MS 2756 GG/AG genotype in the combined hyperlipidemia group was significantly higher than that in the control （26.7% vs 13.0%, P=0.012）, with the OR of 3.121 （95%C1： 1.288-7.65/）. The hyperlipidemia patients with MS 2756AG/GG genotype had a higher concentration of TC （5.87±0.89 mmol/L vs 5.46±0.93 retool/L, P〈0.05） and LDL-C （3.29±0.81 mmol/L vs 2.94±0.85 retool/L, P〈0.05） than those with AA genotype. However, individuals with 2756AG/GG genotype showed no significant difference in tHcy among those with AA genotype. Conclusion HHcy and MS A2756G mutation may be the risk factors for combined hyperlipidemia. Further study is needed to confirm the role of HHcy and MS A2756G mutation in the development of hyperlipidemia.

Association of IL33/ST2 Signal Pathway Gene Polymorphisms with Myocardial Infarction in a Chinese Han Population

This study investigated the relationship between IL-33/ST2 signal pathway gene polymorphisms and myocardial infarction（MI） in Han Chinese. A case-control association analysis was performed on a total of 490 MI patients（MI group） and 929 normal subjects（NC group）. Sequenom Mass Array and Taqman genotyping technique were used to analyze the tag single nucleotide polymorphisms（SNPs） in the genes encoding IL-33, ST2, and IL-1Ra P（rs11792633, rs1041973 and rs4624606）. The results showed that the frequencies of rs4624606 genotypes AA, TT, AT were 0.031, 0.647, 0.322 in MI group and 0.026, 0.712, 0.263 in NC group, and the allele frequencies of A and T were 0.192, 0.808 in MI group and 0.157, 0.843 in NC group. There were significant differences in rs4624606 genotypes and allele frequencies between MI group and NC group（P〈0.05）. For rs11792633, the allele frequencies of C and T were 0.45, 0.55 in MI group and 0.454, 0.546 in NC group with no significant differences found between the two groups. Compared with genotype CC＋TC, rs11792633 genotype TT had an increased risk of hypertension（P〈0.05）. However, there were no significant differences in the frequencies of rs11792633 genotypes between the two groups. No significant differences were noted in the frequencies of rs1041973 genotype and allele between the two groups. Logistic regression analysis showed that rs4624606 genotypes AT and AA＋AT were both significantly associated with MI（AT： OR=1.325, P=0.029, 95% CI=1.03–1.705; AA＋AT： OR=1.316, P=0.028, 95% CI=1.03–1.681） after factors such as age, gender, smoking, drinking, body mass index（BMI）, triglyceride（TG） and cholesterol were adjusted. Those carrying rs4624606 genotype AT or AA＋AT had an increased risk of MI. No associations were found between the polymorphisms of the other two loci with MI. It was concluded that, in the IL33/ST2 signal pathway, the A allele of rs4624606 polymorphism of IL-1Ra P gene is a potential independent risk factor for MI, and the genotypes AA＋AT and AT are associated with the incidence of MI.

Association of vascular endothelial growth factor-634G/C and receptor for advanced glycation end products G82S gene polymorphisms with diabetic retinopathy

AIMTo investigate the association of receptor for advanced glycation end products (RAGE) G82S and vascular endothelial growth factor (VEGF) -634 G/C gene polymorphisms with diabetic retinopathy (DR).METHODSOur cross-sectional study included 61 diabetic patients, 12 of them had proliferative diabetic retinopathy (PDR), 15 had non proliferative diabetic retinopathy (NPDR), 34 had no diabetic retinopathy (NDR) and 61 healthy controls. Participants were tested for RAGE G82S and VEGF -634 G/C polymorphisms by polymerase chain reaction-restriction fragment length polymorphism.RESULTSWe found a significant association between VEGF -634 G/C polymorphism and PDR as PDR patients had increased incidence of VEGF -634 CC genotype compared to NDR patients [odds ratio for CC vs (GC+GG)=6.5, 95% CI=1.5-27.8, P=0.021]. Also VEGF -634 CC genotype and C allele were significantly higher in the PDR than in NPDR patients, which is a novel finding in our study (P=0.024, 0.009 respectively). The mean triglycerides level was significantly higher in diabetic patients with CC genotype (P=0.01) as compared to patients with other genotypes. All cases and control subjects were of the same heterozygous RAGE 82G/S genotype.CONCLUSIONPatients carrying VEGF -634 C polymorphism have a higher risk of PDR development, so VEGF -634 G/C polymorphism could be used as a predictive marker for PDR in diabetic patients. We could not find a significant association between RAGE G82S polymorphism and DR.

Association of glutathione S-transferase T1 and M1 gene polymorphisms with ischemic stroke risk in the Chinese Han population

Atherosclerosis plays an important role in ischemic stroke, and oxidative stress participates in the entire process of atherosclerosis. Glutathione S-transferase （GST） acting with other antioxidant enzymes can eliminate reactive oxygen species and protect cells against oxidative damage. To assess the association of glutathione S-transferase （GSTT1 and GSTM1） gene polymorphisms with ischemic stroke in the Chinese Han population, the present study selected 315 patients with ischemic stroke and 210 healthy controls for comparison. GSTT1 and GSTM1 genotypes were determined using polymerase chain reactions, electrophoresis and imaging analysis. No obvious evidence of GSTTI-nulI, GSTMI-null and GSTTI/GSTMI-double null genotype distribution differences was found between case and control groups or between genders. Subgroup analysis showed that the risk of stroke was increased when hypertension was accompanied by GSTTl-null （odds ratio （OR） = 2.996, P 〈 0.001） and GSTMl-null （OR = 3.680, P 〈 0.001 ） genotypes; diabetes mellitus was accompanied by GSTTI-null （OR = 1.860, P = 0.031） and GSTMI-null （OR = 2.444, P = 0.002） genotypes, and smokers showed a GSTTl-null genotype （OR = 2.276, P = 0.003）. GSTT1- and GSTMl-null genotypes may interact synergistically with hypertension, diabetes mellitus and smoking to increase the incidence risk of ischemic stroke.

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.

Role of CYP2E1 gene polymorphisms association with hepatitis risk in Northeast India

AIM:To investigate hepatitis virus, genetic and environmental factors, and their interactions in predisposing patients to liver diseases in Northeast India. METHODS:A total of 104 jaundice patients and 124 community controls were included. Serological analysis was performed by routine enzyme-linked immunosorbent assay, and nucleic acid testing for hepatitis viruses was done by polymerase chain reaction (PCR), followed by PCR direct sequencing for viral genotyping. Cytochrome P450 2E1 (CYP2E1) polymorphism was studied by PCR-restriction fragment length polymorphism. Nitrite and volatile nitrosamines in indigenous foods consumed routinely by the Northeast Indian ethnic population were estimated by Griess’s reagent and GC-MS, respectively.RESULTS: Hepatitis A virus (HAV) infection was predominantly prevalent (36.5%) in our cohort, followed by hepatitis B virus (HBV), hepatitis E virus (HEV) andhepatitis C virus. HBV genotype D and HEV genotype 1 were the most dominant. CYP2E1 c1/c2 genotype frequency was comparatively higher in alcoholic (P<0.0001,OR =30.5) and cryptogenic (P=0.014, OR=8.714) patients, and was associated with significantly higher hepatitis risk (P=0.0.007,OR=6.489). Mutant C allele of Cyp2E1 DraⅠ frequency was comparatively higher in HAV (P=0.006), alcoholic (P =0.003) and cryptogenic (P=0.014) cases, and was associated with overall hepatitis risk (P=0.026, OR=5.083). Indigenous foods, Gundruk, Kharoli, betel leaf and nuts were found to have the highest nitrite content. CONCLUSION: Apart from viral factors, CYP2E1 polymorphism might be associated with increased risk of liver diseases in Northeast India. Indigenous foods that contain nitrite and nitrosamine might be an associated risk factor.

Association of Bone Turnover Levels with MTHFR Gene Polymorphisms among Pregnant Women in Wuhan, China

Pregnancy is a critical stimulator of bone mineral resorption. We used to find the MTHFR gene polymorphisms are related with blood lead levels among pregnant women. Pregnancy-stimulated bone turnover may be associated with MTHFR gene polymorphisms too. In this article, we aimed to determine the relationship between MTHFR gene polymorphisms and bone turnover rates among the pregnant women. The participants including pregnant and non-pregnant women were selected and recruited during their routine prenatal or physical examination from July to October in 2012. A total of 1000 participants, including 250 pregnant women in the first, second, and third trimesters and 250 non-pregnant women, were enrolled in the study. Finally, after excluding 27 participants unable to provide blood samples, 973 eligible participants （i.e., 234, 249, and 248 pregnant women in the first, second, and third trimesters, respectively, and 242 non-pregnant women） were included in the research. The MTHFR gene 1298CC homozygote carriers were more susceptible to yield higher plasma homocysteine levels than the 1298AA/AC carriers, with standardized coefficients of 0.086 （P〈0.05） and 0.104 （P〈0.01） of all the participants and the pregnant women, respectively. The MTHFR gene 1793AA homozygote carriers more likely showed higher plasma osteocalcin levels （standardized β=0.091, P〈0.01） than the 1793GG/GA carriers among all the subjects. Plasma homocysteine levels were positively correlated with blood lead levels among the participants and the pregnant women with standardized coefficients of 0.320 （P〈0.01） and 0.179 （P〈0.01）, respectively. Plasma osteocalcin levels were positively associated with blood lead levels among pregnant and non-pregnant women with standardized coefficients of 0.084 （P〈0.05） and 0.125 （P〈0.01）, respectively. In conclusion, homocysteine and osteocalcin contents in plasma are associated with the MTHFR gene A1298C polymorphism and blood lead levels among pregnant women. The MTHFR gene A1298C polymorphism-related homocysteine is a possible risk factor for increased blood lead levels among Chinese women.

Association of Vitamin D Receptor Gene Polymorphisms with Calcium Oxalate Calculus Disease

To study the relationship between polymorphism of vitamin D receptor (VDR) allele with formation of calcium oxalate calculus and find the predisposing genes of calcium oxalate calculus, we screened out 150 patients who suffered from calcium oxalate calculus. 36 of them had idiopathic hypercalciuria according to analysis of calculus component and assay of urine calcium. The polymorphisms of VDR gene Taq1, Apa1 and Fok1 were detected using PCR-RFLP technique and the correlation were analyzed between the polymorphism and urinary calculus or between the polymorphism and hypercalciuria. The difference in each genotypic frequency of the allele of promoter Fok1 between calculus group and healthy group or between idiopathic hypercalciuria calculus group and health group was significant. The content of 24-h urine calcium of those who had genotype ff was obviously higher than that of those who have other genotypes in the same group. There was no significant difference in the polymorphism of gene Apa1 and Taq1 between each two groups. It is concluded that hypercalciuria and calcium oxalate calculus were related to the polymorphism of VDR gene's promoter Fok1 allele, but it had nothing to do with the polymorphism of gene Apa1 and Taq1. The genotype ff was a candidate heredity marker of calcium calculus disease.