PRDM16基因单核苷酸多态性与肥胖人群血脂异常的相关性

Polymorphism of PRDM16 gene:effect on dyslipidemia in obese patients

目的：探讨PRDM16基因与新疆维吾尔族肥胖患者血脂异常的关系。方法：采用毛细管电泳法对36例BMI≥30kg/m2个体进行PRDM16启动子区及外显子区测序,筛查该基因功能区的变异位点。选择有代表性变异位点,在533例新疆维吾尔族肥胖人群中进行基因型鉴定。采用病例对照的方法分析PRDM16基因变异与该人群的血脂异常之间的关系。结果：在PRDM16基因的功能区发现21个变异位点,其中rs2236518、rs2493292、rs2282198和rs8170171位点成功进行了基因型鉴定。rs2282198的基因型频率在高胆固醇血症组和对照组（P=0.04）及低高密度脂蛋白胆固醇组和对照组（P=0.006）之间分布差异有统计学意义。rs2236518的基因型频率在低高密度脂蛋白胆固醇组和对照组之间分布差异有统计学意义（P=0.015）。校正混杂因素后Logistic回归分析显示,rs2282198的CT＋TT基因型是高三酰甘油血症（OR：1.789,95%CI：1.159~2.762,P=0.008）及低高密度脂蛋白胆固醇血症（OR：0.539,95%CI：0.350~0.830,P=0.005）的独立危险因素。数量表型分析显示,校正混杂因素后,rs2282198的CT＋TT基因型携带者血清HDL-C显著低于CC携带者（P=0.021）。结论：PRDM16基因的变异位点rs2282198与新疆维吾尔族肥胖者的血脂异常相关。

Objective：To analyze the association between the genetic variations of functional region in PRDM16 gene and dyslipidemia in Uygur obese subjects. Method： We screened the promoter and all exons of the PRDM16 gene in 36 Uygur obese individuals to identify representative variations. Genotyping was performed in 533 Uygur obese individuals. A case-control study was conducted to test the association between variants of PRDM16 and dyslipidemia. Result：Twenty-two variants were identified and 4 SNPs were genotyped. The SNP, rs2282198 has significantly different genotype frequencies between case and control subjects （P= 0.04 for hypercholesterolemia） and （P=0. 006 for low HDL-C）. The significance was also observed for rs2236518 between hypercholesterolemia and control groups （P =0. 015）. Logistic regression tests showed the CTTTT genotypes of rs2282198 was the independent risk factor of hypercholesterolemia （OR： 1. 789, 95%CI= 1. 159--2. 762, P=0. 008） and low HDL C （OR： 0.539, 95%CI： 0.350--0.830, P=0.005）. The quantitative trait analyses showed the effect ofrs2282198 on serum HDL-C （P=0. 021 after adjustment for confound factors）. Conelusion： In the obese people, variant in PRDM16 gene may have some effect on lipid metabolism and cause variation in serum lipid concentrations.