丝裂原活化蛋白激酶激活蛋白激酶2基因多态性与新疆维吾尔族人代谢综合征易感性的研究

目的 研究丝裂原活化蛋白激酶激活蛋白激酶2(MK2)基因是否与代谢综合征(MS)有关联,为探讨MS的分子遗传基础提供依据.方法 采取以流行病学调查为基础的病例对照研究,选择2334例维吾尔族自然人群(MS组808例,非MS组1526例)作为研究对象.首先测序筛查维吾尔族MS患者MK2基因功能区的变异位点,然后选择代表性变异位点应用TaqMan-PCR在大样本人群中进行基因型鉴定及病例对照关联研究.结果 在MK2基因功能区共发现7个变异位点(4个已知变异位点,3个新发现的变异位点),选取3个代表性变异位点进行基因型鉴定.TaqMan-PCR分型成功的2个变异位点(rs45514798、44890c/t)的基因型频率在MS组和非MS组的分布差异均无统计学意义(均为P＞0.05).然而,rs45514798位点GG基因型的腰围(85.1+11.5)cm低于(AG+AA)基因型(87.1+21.7)cm,差异有统计学意义(t=2.145,P=0.032).单体型关联分析发现H3 C-A在MS组的频率(12.9％)高于非MS组(10.3％),差异有统计学意义(x2=4.326,P=0.035)；H3 C-A单体型在女性人群MS组的频率(13.9％)高于非MS组(10.8％),差异有临界统计学意义(x2=3.79,P=O.050).结论 MK2基因rs45514798、44890c/t位点变异与新疆维吾尔族人MS无关联；而rs45514798位点与腰围的关系有待进一步验证.

Association between genetic variation of mitogen-activated protein kinase activated protein kinase 2 gene and metabolic syndrome in Uygur population

Objective To examine the association between mitogen- activated protein kinaseactivated protein kinases 2 (MK2) gene variation and metabolic syndrome (MS),so as to provide evidence for molecular genetics study on MS.Methods In this epidemiologic survey-based case-control study,2334Uygur subjects from natural population were enrolled (808 people with MS and 1526 without MS).Genetic variations were sequenced and screened at loci over functional region of MK2 gene in MS subjects.The typical loci were selected for genotyping by TaqMan-PCR method in 2334 Uygur subjects for case-control study.Results Three typicalloci out of the 7 variation loci (4 already known and 3 newly founded)identified at the functional region of MK2 gene were selected for genotyping.There was no statistical difference in genotypic frequency of 2 TaqMan-PCR-identified variation loci (rs45514798,44890c/t)between MS group and non-MS group (P＞0.05).However,subjects with GG genotype at rs45514798 had significantly smaller waist circumference (85.1 + 11.5)cm ] than those with genotypes AG or AA (87.1 +21.7)cm] (t=2.145,P=0.032).According to haplotype association analysis,the frequency of H3 C-A in MS group (12.9％) was higher than that in non-MS group (10.3％) (X2=4.326,P=0.035),and higher in MS females (13.9％) than in non-MS females (10.8％) (x2=3.79,P=0.050).Conclusion Among Urgur population,the polymorphisms of the MK2 gene 44890c/t and rs45514798 are not associated with MS,while the association between waist circumference and rs45514798 polymorphism remains to be further confirmed.