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Association between Genetic Variations of Six-transmembrane Protein of Prostate2(STAMP2) and Metabolic Syndrome in Xinjiang Uygur Population

Author: HanRuiMei
Tutor: LiNanFang
School: Xinjiang Medical University
Course: Internal Medicine
Keywords: Genetic epidemiology Genetic association study Metabolic syndrome Uygur STAMP2gene
CLC: R589
Type: PhD thesis
Year: 2012
Downloads: 34
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Objective: To investigate the prevalence of Metabolic syndrome (MetS) in Uygur.Systematically screen for and examine SNPs of six-transmembrane protein of prostate2(STAMP2) in Uygur ethnic groups and the pattern of intragenic linkage disequilibriumand the haplotype structure were estimated. Then explore the relation between variation ofSTAMP2polymorphisms and MetS in a large cohort from general Uygur population. Weaim to demonstrate effect of candidate genes in MetS pathogenesis from geneticperspectives and further investigate the mechanisms in more polulations.Methods:Subjects were selected from the cross-sectional study of obesity, hypertension,diabetes mellitus, dyslipidemia among Uygur1545individuaIs with aged30-70years inHETIAN area of Xinjiang (male588and female957) based on the epidemiology. Basedon the criteria of international diabetes federation (IDF), there were858MetS subjects.The sequences of the putative promoter region, exon-intron boundaries,and all exons,including the5’-and3’-untranslated regions(UTRs)(~lkb) of STAMP2gene were PCRamplified and sequenced in96Uygur MetS subjects (including48males and48females).Representative variations were selected with linkage disequilibrium (a r2cutoff of0.8),minor allele frequency of>5%and possible function (missense mutation) were genotypedwith TaqMan-PCR method in all subjects,and then constructed a case-control study.Statistical analyses were performed using SPSS version16.0software package. Betweencase and control groups, distributions of patient characteristics, allele and genotypesfrequency of each SNPs were analyzed using the t-test or Chi-square test. Adjusted Oddsratios(ORs) with95%confidence intervals from logistic regression analysis was used toestimate the relative risk of MetS associated with genotype: linkage disequilibrium (LD)analysis was carried out in a pair-wise fashion, the determination of haplotype block andthe estimation and comparation of haplotypes frequencies in two groups were inferred bythe SNPalyzer7.0Pro package. Results:(1)Epidemiology survey result indicated that the prevalence of MetS was55.5%from HeTian Area of Xinjiang in Uygur population.Respectively, prevalence of hypertension, abdominal obesity, hyperglycemia, and bloodlipid disorders were47.5%,40.4%,35.9%and31.6%. The detection rate was highest in40-50years and in female was more than in male. Gender and drinking were the majorrisk factor of MetS.(2)We identified20variations,including14novel variations and6known variations (including2nonsynonymous SNPs) of the STAMP2gene by sequencingin96Uygur patients with MetS. Accounting of linkage disequilibrium relationships andfunctions, five representative variations:224A/G(rsl981529, Gly75Asp),364G/A(rs34741656, Alal22Thr),7414G/A(rs8122),-237a/c and6031T/G (unsuccessfullygenotyped) were genotyped in a large cohort from epidemiological study.(3)The variation-237a/c with MAF<5%was genotyped in1110subjects and found25individuals with acgenotype and found no individuals with CC genotype. The variation-237a/c wasdistributed in the cases and controls of MetS, and was not special for the prevalence ofMetS and its related phenotypes. Of the other3common variations, rs8122(Padditive=0.032)and rsl981529(Padditive=0.011) were significantly associated with MetS phenotype inUygur female populations.By the multiple linear regression analysis controlling age anddisease status confound factors, the significant association of the variations rs8122andrs1981529with HDL-C level in IDF defined-MetS cases (P=0.001,0.024, respectively)and in a combined sample (case+control)(P=0.004,0.009, respectively) were revealed,and the mean values of HDL-C level were gradual decline among A (protection) allelecarriers of rs8122and among G (protection) allele carriers of rs1981529in both MetScases and the combined sample.The association between haplotypes of the STAMP2genepolymorphisms and MetS was further performed. Haplotype (G-A-G)(rs8122-rsl981529-rs34741656) were associated with a higher prevalence of MetS(Permutation P=0.044) and haplotype (A-G-G)(rs8122-rsl981529-rs34741656) wasassociated with a lower prevalence of MetS (Permutation P=0.009) in Uygur female.Conclusion:The prevalence of MetS and and its components were higher in XinjiangUygur population. The detection rate was highest among age40to50, and the prevalenceof MetS in male Uygur population was significantly lower than in female. STAMP2genetic variations are likely to be associated with metabolic syndrome of female Uygur.

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CLC: > Medicine, health > Internal Medicine > Endocrine diseases and metabolic diseases > Metabolic diseases
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