激活转录因子6基因Ala145Pro变异与中国人糖脂代谢的关联研究

Investigation on association of activating transcription factor 6 Ala145Pro variant with glucose and lipid metabolism in Chinese

目的研究激活转录因子6(ATF6)基因Ala145Pro(GCG→CCG)变异与中国人糖脂代谢的相关性。方法对689例上海地区中国人(其中糖调节正常者361名,新诊断2型糖尿病患者250例,早发2型糖尿病家系先证者78例)采用PCR-RFLP检测ATF6基因Ala145Pro变异,并测定所选人群的糖脂代谢相关临床指标。结果(1)等位基因频率分布在早发2型糖尿病家系先证者和糖调节正常人群中差异有统计学意义(P=0.035),糖调节正常人群中C等位基因频率较高;(2)糖调节正常人群中,CC+CG基因型携带者高密度脂蛋白胆固醇较GG基因型者低(P=0.014);(3)新诊断2型糖尿病患者中,CC+CG基因型携带者低密度脂蛋白胆固醇较GG基因型者高(P=0.041)。结论ATF6基因与中国人糖脂代谢相关。

Objective To investigate the association of activating transcription factor 6 （ATF6） gene Ala145Pro （GCG→CCG） variant with glucose and lipid metabolism in Chinese. Methods The genotypes were determined by PCR-RFLP in 689 Chinese in Shanghai. Among them, 361 subjects showed normal glucose regulation, 250 cases were newly-diagnosed diabetic patients without taking any drug and 78 cases were probands of early-onset type 2 diabetes pedigrees. The following phenotypes were measured： body height and weight to calculate BMI; waist, hip and femoral circumference to calculate waist-to-hip ratio and waist-to-femoral ratio; blood pressure; plasma glucose levels obtained at 0 and 120 minute during 75 g oral glucose tolerance test; fasting serum lipid profile including total cholesterol, triglyceride, high density lipoprotein-cholesterol and low density lipoprotein-cholesterol; body fat percentage and distribution. Results （1） The frequency of C allele is significantly lower in probands from early-onset type 2 diabetes patients compared with subjects with normal glucose regulation （ P = 0.035 ）. （ 2 ） In subjects with normal glucose regulation, the CC ＋ CG genotype had a significantly lower level of high density lipoprotein cholesterol as compared with GG genotype （ P = 0. 014 ）. （ 3 ） In type 2 diabetic patients, the CC ＋ CG genotype had a significantly higher level of low density lipoprotein-cholesterol as compared with GG genotype （ P = 0.041 ）. Conclusion These findings suggest that variant of ATF6 plays a role in glucose and lipid metabolism in Chinese.