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.

Maternal TMPRSS6 Gene Polymorphism rs855791SNP in Women with Preeclampsia

Introduction: Preeclampsia can lead to several maternal and perinatal adverse effects. There are few published data on the association between transmembrane serine protease 6 (TMPRSS6) gene polymorphism and preeclampsia. Objective: To assess the association between TMPRSS6 gene polymorphism rs855791SNP in women with preeclampsia compared with healthy pregnant women. Method: A case-control study (60 women in each arm) was conducted at Saad Abuaela Maternity Hospital in Khartoum, Sudan. Sociodemographic and clinical data were gathered through a questionnaire. The participant was genotype for TMPRSS6 gene rs855791SNP using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP). The results were confirmed by DNA sequencing. Result: There was no significant difference in the median of age, parity, and body mass index. The distribution of the genotypes and alleles of TMPRSS6 rs855791 was consistent with the HWE. The overall TMPRSS6 rs855791 polymorphism was not significantly associated with preeclampsia. However, the proportion of heterozygotes (TC) was considerably higher in the women with preeclampsia (46.7%) than in the control group (23.3%) (p = 0.001;OR = 2.71;95% CI = 1.21 - 6.07). The proportion of homozygotes (TT) and T alleles was not significantly different between women with preeclampsia and the control group. Conclusion: The overall TMPRSS6 rs855791 polymorphism was not significantly associated with preeclampsia and healthy control.

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.

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.

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.

Job Stress, Gene Polymorphism of β_2-AR, and Prevalence of Hypertension

Objective To study the interactive effect of job stress and genetic susceptibility （or gene polymorphism） on hypertension. Methods A cross-sectional epidemiological study was conducted in 452 workers from a thermal power plant in China. Extrinsic effort, occupational reward, and over-commitment were measured. Hypertensive patients were defined by three phases of screening, reexamination, and final diagnosis. β2-AR genotypes and allele frequencies at amino acid positions 16 （β2-AR-16： Arg→Gly） and 27 （β2-AR-27： Gln→Glu） were identified by PCR-RFLE Results Job stress was related with the prevalence of hypertension in males （P〈0.05）, whereas no significant relationship was found in females （P〉0.05）. Differences in genotypes and allele frequencies of the β2-AR-16 were statistically significant between the hypertension and control groups （P〈0.05）, whereas those of β2-AR-27 were not （P〉0.05）. The prevalence of hypertension was higher in individuals carrying Gly16 allele than in those carrying Arg16 allele of the high job stress group （P〈0.01 or 0.05）. Conclusion High job stress and polymorphism of β2-AR-16 have an interactive effect on the prevalence of hypertension in male workers.

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.

Relationship between granulomatous lobular mastitis and methylene tetrahydrofolate reductase gene polymorphism

BACKGROUND Variations in the methylene tetrahydrofolate reductase(MTHFR)gene have been reported as risk factors for numerous conditions,including cardiovascular disease,thrombophilia,stroke,hypertension and pregnancy-related complications.Moreover,it was reported there is an association between breast cancer and mutations in MTHFR-C677T.However,whether there is an association between MTHFR gene polymorphism and granulomatous lobular mastitis or not has been rarely investigated.AIM To analyze the association between MTHFR gene polymorphism and granulomatous lobular mastitis.METHODS Fifty-one patients with granulomatous lobular mastitis admitted to The First Hospital of Kunming were selected as study samples.Their hospitalization time ranged from February 2018 to February 2019.The 51 patients were included in the experimental group,and another 51 women who underwent physical examination at The First Hospital of Kunming in the same period were included in the control group.Deoxyribonucleic acid and MTFR genetic polymorphism testing were performed in each group.The association between MTHFR gene polymorphism and granulomatous lobular mastitis was observed.RESULTS There were significant differences in genotype frequency and allele frequency of C/C and C/T between the experimental group and the control group(all P<0.05).However,there was no significant difference in frequency of T/T genotype between the two groups(P>0.05).In addition,there was no significant difference in genotype frequency and allele frequency of A/A,A/C and C/C between the two groups(P>0.05).CONCLUSION MTHFR gene C677T locus polymorphism is closely related to granulomatous lobular mastitis.

Methylenetetrahydrofolate Reductase Gene Polymorphism C677T is Associated with Increased Risk of Coronary Heart Disease in Chinese Type 2 Diabetic Patients

Objective Chronic cardiovascular diseases induced by long-term poor blood glucose control are the main cause of death in patients with type 2 diabetes mellitus(T2DM).Previous researches report that methylenetetrahydrofolate reductase gene(MTHFR)polymorphisms might influence the occurrence of coronary heart disease(CHD)in T2DM patients.The purpose of this study was to evaluate whether MTHFR C677T and A1298C mutations are associated with the risk of CHD inT2DM patients.Methods A total of 197 subjects with T2DM were studied,of which 95 patients with CHD.The genotypes of MTHFR C677T and A1298C were analyzed by using dideoxy chain-termination method,and compared between patients with CHD and those without CHD.Results We found that the frequency of the 677T allele was significantly higher in T2DM patients with CHD than those without CHD(P=0.011).However,there was no significant difference in any of the examined haplotypes between T2DM patients with and without CHD.Furthermore,the 677T allele was associated with a higher risk of CHD development in diabetic patients with lower homocysteine(Hey)levels(≤15μmol/L)(P=0.006),while no effect of MTHFR gene polymorphism on the incidence of CHD was found in patients with higher Hey levels(>15 μmol/L)(P=0.491).Conclusion The MTHFR C677T gene polymorphism is associated with the risk of CHD of diabetic patients and could be used as an effective marker for CHD in Chinese diabetic populations with normal Hey levels.

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.

Androgen receptor gene polymorphism and sex hormones in elderly men:the Tromsøstudy

The aim of this study was to examine whether CAG/GGN repeats are significant modulators of serum concentrations of total and free testosterone(T)as well as of luteinizing hormone(LH)in elderly men.Sixty-nine 60-to 80-year-old men with subnormal T levels(≤11.0 nmol L^(-1))and 104 men with normal T levels taking part in a nested case-control study were used for these analyses.Sex hormones were measured and free T was calculated.The CAG and GGN polymorphisms in the androgen receptor gene were determined by polymerase chain reaction and subsequent direct sequencing.There were no differences in the CAG and GGN repeat lengths between the groups.In cross-sectional analyses of the whole cohort,total and free T were positively associated with CAG length(all P<0.05)before,but not after,waist circumference or body mass index was added to the model.CAG repeat lengths were weakly,but not independently,associated with total and free T.These findings indicate that when clinically evaluating T and LH levels in elderly men,the CAG and GGN repeat lengths do not need to be taken into consideration.

Relationship between catecholamine level and gene polymorphism of β1 adrenergic receptor G1165C in children with EV71 infection in hand foot and mouth disease

Objective:To investigate the relationship between the levels of plasma adrenaline and norepinephrine and gene polymorphism of β1 adrenergic receptor G1165 C in children with enterovirus 71(EV71) infection in hand foot and mouth disease(HFMD). Methods:The polymerase chain reaction(PCR) was used to detect the expression of gene polymorphism of β1 adrenergic receptor G1165 C in vitro. The levels of plasma adrenaline and norepinephrine were measured by enzyme-linked immunosorbent assay(ELISA). Results:The plasma norepinephrine level of severe group was significantly higher than the mild group in children with EV71 infection in HFMD(P<0.05); however,the levels of plasma adrenalinein in two groups had no statistical differences(P>0.05); There was no significant difference in the distribution of β1 adrenergic receptor G1165 C genotype and allele between EV71 infection group and healthy control group(P> 0.05). Further analysis of EV71 infection group by dividing it into mild and severe groups showed that there was no significant difference in the distribution of genotype and allele between these two groups as well(P> 0.05). There was no significant difference in the levels of epinephrine and norepinephrine in different genotypes of EV71 infection group(P> 0.05),and in the levels of plasma epinephrine and norepinephrine in the mild and severe groups(P> 0.05). Conclusions:As the disease gets worse,the plasma norepinephrine level has a rising trend in children with EV71 infection in HFMD,which is an important indicator to evaluate the progress of the disease. However,the gene polymorphism of eptor G1165 C have no significant correlation,not only with the susceptibility and severit β1 adrenergic recy of EV71 infection in hand,foot and mouth disease,but also with the levels of catecholamine.

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.

Interleukin-8 gene polymorphism is associated with acute coronary syndrome in a Han Chinese population

Background Acute coronary syndrome(ACS) is one of the most common forms of heart diseases.Recent studies have revealed that interleukin(IL)-8 plays a kev role in the development of atherosclerosis plaque and its complications, but the relationship of its common variants with ACS has not been extensively studied.Methods We tested the hypothesis that variants in IL-8-251 A/T was associated with susceptibility to ACS and its recurrence in a Chinese case-control study comprising 675 patients with ACS and 636 control subjects and replicated the investigation in an independent study comprising 360 cases and 360 control subjects. The plasma concentration of IL-8 was measured by enzyme-linked immunosorbent assay.Results IL-8 -251A】T poly-morphism was associated with increased susceptibility to ACS (P=0.004;OR=1.30 CI:1.12-1.53).Replication in the second study yielded similar results.IL-8 -251 A/T may affect the expression of IL-8 by the evidence that augmented IL-8 production revealed in serum of the AMI patients by ELISA. Conclusions IL-8 -251 A/T polymorphism is associated with ACS risk in Chinese Han population and An allele of IL-8- 251A/T may be an independent predictive factor.

Meta-analysis of 5, 10-methylenetetrahydrofolate reductase gene polymorphism as a risk factor for ischemic cerebrovascular disease in a Chinese Han population

OBJECTIVE： To assess whether 5, 10-methylenetetrahydrofolate reductase （MTHFR） gene polymorphism （TT genotype or T allele） is a risk factor for ischemic cerebrovascular disease （ICVD）. DATA SOURCES： MEDLINE and PubMed databases from September 1997 to December 2009 were searched for case-control studies that examined MTHFR genotype in human ICVD using ＂MTHFR, gene, polymorphism, and ischemic cerebrovascular disease＂ as search key words. STUDY SELECTION： Eighteen associated studies were identified. The methods used to collect relevant information factors were similar between case and control groups, and diagnosis of ischemic cerebrovascular disease was in accordance with Trial of ORG 10172 in Acute Stroke Treatment criteria classification, with some referring to European Stroke Diagnostic Criteria. Quality of all included studies was evaluated, and meta-analysis was conducted using RevMan4.2 software （Cochrane Collaboration, http：//www.cochrane-handbook.org） following strict screening. MAIN OUTCOME MEASURES： The correlation between MTHFR gene TT genotype or T allele and ICVD was determined. RESULTS： Eighteen studies involving 4 295 patients with ICVD and 6 169 control subjects were included for this meta-analysis. There was a significant difference in MTHFR gene TT genotype or T allele frequency （x^2 = 15.737, 9.186, P 〈 0.01） between ICVD cases and controls. In addition, six Chinese Han population studies were specially reviewed by meta-analysis. Results showed no significant difference between ICVD and control groups with regard to frequency of MTHFR gene TT genotype and T allele （x^2 = 1.076, 2.434, P 〉 0.05） in the Chinese Han population. CONCLUSION： Results from the present meta-analysis suggested that the MTHFR gene TT genotype or T allele is a risk factor for ICVD. However, the TT genotype or T allele is not a risk factor for ICVD in the Chinese Han population.

Fluoride Exposure,Follicle Stimulating Hormone Receptor Gene Polymorphism and Hypothalamus-pituitary-ovarian Axis Hormones in Chinese Women

The effects of fluoride exposure on thefunctions of reproductive and endocrine systemshave attracted widespread attention in academiccircle nowadays. However, it is unclear whether thegene-environment interaction may modify thesecretion and activity of hypothalamus-pituitary-ovarian （HPO） axis hormones. Thus, the aim of thisstudy was to explore the influence of fluorideexposure and follicle stimulating hormone receptor（FSHR） gene polymorphism on reproductivehormones in Chinese women. A cross sectionalstudy was conducted in seven villages of HenanProvince, China during 2010-2011. A total of 679women aged 18-48 years were recruited throughcluster sampling and divided into three groups, i.e.endemic fluorosis group （EFG）, defluoridationproject group （DFPG）, and control group （CG） basedon the local fluoride concentration in drinkingwater. The serum levels of gonadotropin releasinghormone （GnRH）, follicle stimulating hormone（FSH）, luteinizing hormone （LH）, and estradiol （E2）were determined respectively and the FSHRpolymorphism was detected by real time PCR assay.The results provided the preliminary evidenceindicating the gene-environment interaction onHPO axishormones in women.

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.