SOCS3、STEAP4、MK2和ZFP36基因间及基因-环境交互作用与新疆维吾尔族人群高血压的关联研究

Association Study between Interactions of SOCS3,STEAP4,MK2 and ZFP36 Gene and Gene-environment and Essential Hypertension in Uygur Population of Xinjiang

目的研究SOCS3、STEAP4、MK2和ZFP36基因间及基因一环境交互作用与新疆维吾尔族人群高血压的相关性。方法采取以流行病学调查为基础的病例对照研究，选取872例维吾尔族自然人群（高血压组399例，正常对照组473例）作为研究对象。首先对STEAP4、MK2及ZFP36进行测序筛查维吾尔族高血压患者的基因变异位点，然后选择出代表性变异位点，而SOCS3基因则是查阅文献后直接选择代表性的标签SNPs，之后应用TaqMan-PCR基因型鉴定和病例对照研究，并结合多因子降维法（multifactordimentionalityreduction，MDR）分析基因一基因、基因一环境的交互作用。结果4个基因的10个TagSNPs变异位点的基因型分布均符合Hardy-Weinberg平衡定律（P〉0．05）。在高血压及对照组中SOCS3基因rs9914220位点及STEAP4基因rs8122位点基因型频率分布有差异（X2=7．07，P=0．029；矿=8．631，P=0．013）。单体型分析发现SOCS3基因H4G-C-A在对照组的频率高于高血压组（10．47％VS6．58％％），差异有统计学意义（P=0．006）。MDR结果显示，在所有模型中，SOCS3rs9914220基因和超重肥胖交互作用检验准确性最高，为61．58％，交叉验证一致性为10／10，P=0．001。应用Logistic回归分析校正性别、年龄、空腹血糖、TC、TG等影响因素后显示，SOCS3基因rs9914220（CC＋CT）合并BMI作用增加新疆维吾尔族人群高血压发生风险（OR=1．025，95％CI：1．002-1．049，P=0．033）。结论SOCS3基因rs9914220（CC＋CT）合并超重肥胖时可能进一步增加新疆维吾尔族人群高血压的风险。

Objective To investigate the association between interactions of SOCS3,STEAP4,MK2 and ZFP36 gene and gene - en- vironment and essential hypertension in Uygur population of Xinjiang. Methods In this epidemiologic cross - sectional study,872 Uygur individuals from natural population were enrolled（399 people with hypertension and 473 without hypertension）. Genetic variations were se-quenced and screened of STEAP4, MK2 and ZFP36 in hypertension subjects,but representative variations of SOCS3 were selected accord- ing to gene database. And then, all the genotyped using the TaqMan polymerase chain reaction method in 872 Uygur individuals and a ease - control study was conducted to test the association between the genetic variations of the 4 genes and hypertension. Based on the idea of data mining,the multifactorial dimention reduction（MDR） method was used to estimate the best model for synergic effect on hypertension. Results All genotype distributions were tested for deviations from Hardy - Weinberg equnilibrium （P 〉 0.05 ）. There were significant differences of genotype of rs9914220 in SOCS3 gene and rs8122 in STEAP4 gene between hypertension and control groups（x2 = 7.07 ,P = 0.029;Xz = 8. 631, P = 0. 013）. According to haplotype association anlysis, the frequency of H4 G- C -A in hypertension group （10.47% ）was higher than that in control group （6.58%, P = 0. 006）. We used M DR to investigate the association between interactions of SOCS3, STEAP4, MK2 and ZFP36 gene and gene -environment and essential hypertension. In all models, the testing accuracy of the inter- action between rs9914220 in SOCS3 gene and overweight/obesity was highest（61.58% ） , and the crossvalidation consistency was 10/10 （P = 0. 001 ）. The logistic regression analysis showed that the interaction between rs9914220 （CC ＋ CT） in SOCS3 gene and overweight/ obesity might be the risky factors for hypertension（OR = 1.025,95% CI：1.002 - 1.049,P =0.033）. Conclusion The individuals carrying （CC ＋ CT） genotype of rs9914220 in SOCS3 gene will greatly increase the risk of hypertension once the overweight/obesity was combined.