摘要
目的本研究在前期流行病学基础上探讨编码G-蛋白偶联内向整流钾通道4的KCNJ5基因单核苷酸基因多态性(SNPs)在新疆维吾尔族代谢综合征的分布特点,探讨KCNJ5基因SNPs及单体型与新疆维吾尔族代谢综合征的关系,寻找新疆维吾尔族代谢综合征的易感性标记,探讨代谢综合征可能的遗传学机制。方法选取48例典型代谢综合征患者(男女性各24例)进行测序筛查新疆维吾尔族Met S患者KCN J5基因功能区的变异位点,寻找常见和罕见或低频率变异。选择代表性单核苷酸多态(SNP)变异位点5个,4个为常见SNPs,-20559C>G(rs11221497),171C>T(rs6590357,Ser57Ser),5126A>G(rs4937391),6262A>C(rs2604204),应用Taq Man-PCR在自然人群中进行基因型鉴定及病例对照关联研究。结果在新疆维吾尔族人群对KCNJ5基因常见SNPs即-20559C>G(rs11221497),171C>T(rs6590357,Ser57Ser),5126A>G(rs4937391)及6262A>C(rs2604204)做基因型鉴定并对上述SN Ps与代谢综合征做病例对照关联研究,显示:(1)-20559C>G(rs11221497)基因型及等位基因的频率在代谢综合征和非代谢综合征组两组间均有统计学差别。控制了年龄、性别等混杂因素后,-20559C>G(rs11221497)多态性与代谢综合征的关系仍有统计学意义。携带G等位基因患者代谢综合征的相对风险率比携带C等位基因者低。(2)-20559C>G(rs11221497)的不同基因型与代谢综合征表型数量性状有关,GG基因型携带者较CC基因型携带者有更低的腰围、总胆固醇水平及血压水平。(3)171C>T(rs6590357),5126A>G(rs4937391)及6262A>C(rs2604204)多态性与代谢综合征关联分析无统计学差别,可能上述三个位点变异与新疆维吾尔族代谢综合征无关。结论维吾尔族人群KCNJ5基因存在变异,而启动子区-20559C>G(rs11221497)的SNP与新疆维吾尔族人代谢综合征相关。进一步可考虑行功能试验以验证。
Objective Recently, researchers reported that G protein-coupled inward rectifier K＋ channels 4 gene（GIRK4,KCNJ5）is involved in the development of obesity, which is a key component of MetS. Meanwhile, studies showed that the prevalence of MetS in Xinjiang Uygur population is the higher than other ethnic groups in China. Therefore, based on our previous epidemiologic study, a case-control study was conducted to screen the genetic variations in KCNJ5 in Uygur Chinese patients with MetS and to analyze the association between the representative genetic variations of Girk4 gene and MetS in Xinjiang Uygur population. Methods We sequenced all exons and the promoter regions of KCNJ5 in 48 typical MetS individuals and identified 21 genetic variations of KCNJ5. Genotyping by the Taq Man polymerase chain reaction method was performed for four representative common single nucleotide polymorphisms（SNPs,-20559 g〉c rs11221497, 171 T〉C rs6590357, 5126 g〉a rs4937391, 6262 A〉C rs2604204） and one missense mutation（630 G〉A,Met210 Ile）in the general population, with a sample size of 1352 individuals. A case-control association study（MetS criteria defined by CDS,including 443 MetS and 786 non-MetS） was used to study the associations of genetic variations in GIRK4. Results A case-control association analysis revealed that there were a significant association for rs11221497 in the dominant model and the allele model（P=0.03 and P=0.04 respectively）; OR（95%CI） in the dominant mode was 0.73（0.55-0.97）, After adjusting for age and gender, multivariate logistic regression analysis also showed that rs11221497 in both the dominant and the additive model were significantly associated with MetS.rs11221497 G-allele was a protective factor of the development of MetS.（2）There was a significant relationship between the polymorphisms of rs11221497 and various MetS quantitative phenotypes. Individuals with GG genotype had lower WC, TC, SBP and DBP（P =0.051,P=0.042,P=0.003 and P=0.007 respectively.（3）No significant difference between rs6590357, rs4937391, rs2604204 and MetS in total population were detected. It implicated there were no relationship between SNPs rs6590357, rs4937391, rs2604204 and MetS. Conclusion There are first reports about the association study between genetic variations of KCNJ5 gene and human complex diseases. The present study suggested that Girk4 might be a candidate gene of human MetS. Rs11221497 may be an independent risk factor for MetS in Xinjiang Uygur population and the findings implicated the rs11221497 G-allele was a protective factor and the rs6590367 T-allele may contribute to the development of MetS.
作者
张德莲
周玲
洪静
胡君丽
李南方
ZHANG Delian;ZHOU Ling;HONG Jing;LI Nan-fang(The Center for Hypertension of the People＇s Hospital of Xinjiang Uygur Autonomous Regio;Hypertension Institute of Xinjiang, grumuqi 830001,Chin)
出处
《新疆医学》
2018年第4期351-356,共6页
Xinjiang Medical Journal
基金
国家自然科学基金地区科学基金项目(81460078)
