SLC12A3基因Arg913Gln多态与上海地区汉族人群T2DM肾病的关系

目的 探讨溶质载体家族12成员3（SLC12A3）基因Arg913Gln（G→A）多态与上海地区汉族人群2型糖尿病（T2DM）及糖尿病肾病（DN）的相关性。方法 上海地区258例汉族T2DM患者（T2DM组）根据24 h尿白蛋白排泄率（AER）分为未合并肾病组（DN0组，n=95）和合并肾病组（DN组，n=163），后者又分为微量蛋白尿肾病亚组（DN1组，n=95）和显性蛋白尿肾病亚组（DN2组，n=68）；以无糖尿病和肾病且口服葡萄糖耐量试验（OGTT）正常者作为对照组（n=82）。应用PCR直接测序法检测各组多态基因型；比较各组间基因型、等位基因频率及临床变量间的差异。结果 检出多态基因型GG、GA和AA。T2DM组的多态基因型和等位基因频率高于对照组，但差异无统计学意义（P>0.05）；T2DM组各亚组间多态基因型和等位基因频率比较差异亦无统计学意义（P>0.05）。T2DM组GA+AA基因型患者的三酰甘油（TG）、AER、空腹血胰岛素（FINS）和HOMA IR值均显著高于GG基因型患者（均P<0.05）。结论 上海地区汉族人群SLC12A3基因Arg913Gln（G→A）多态与T2DM和DN无显著相关性；GA+AA基因型携带者的AER显著高于GG基因型携带者。提示Arg913Gln多态（G→A）可能是中国上海地区汉族T2DM患者蛋白尿显著增加的一个标志。

Relationship between SLC12A3 gene Arg913Gln polymorphism and type 2 diabetic nephropathy in Han population of Shanghai

Objective To explore the relationship between Arg913Gln(G→A) polymorphism of solute carrier family 12 member 3 (SLC12A3) gene and diabetic nephropathy (DN) in type 2 diabetes mellitus (T2DM) in Han population of Shanghai. Methods Two hundred and fifty-eight Han ethnic people in Shanghai with T2DM (T2DM group) were divided into non-DN group (DN0 group, n=95) and DN group (n=163) according to 24 h urine albumin excretion rate (AER), and those in DN group were subdivided into microalbuminuria group (DN1 group, n=95) and macroalbuminuria group (DN2 group, n=68). Besides, 82 people with normal results of oral glucose tolerance test (OGTT), without diabetes mellitus and nephropathy were served as controls. PCR-sequencing was used to detect the genotypes of Arg913Gln polymorphism of SLC12A3 gene. Genotypic and allelic frequencies and clinical characteristics were compared among groups. Results Three genotypes (GG, GA and AA) were detected. The frequencies of GA+AA genotype and A allele in T2DM group were higher than those in control group, while there was no significant difference between groups (P>0.05). There was no significant difference in genotypic or allelic frequencies among subgroups of T2DM group (P>0.05). The level of triglyeeride (TG), AER, level of fasting insulin (FINS) and HOMA-IR in patients with GA+AA genotype were significantly higher than those in patients with GG genotype in T2DM group (P<0.05). Conclusion Arg913Gln(G→A) polymorphism of SLC12A3 gene is not significantly associated with T2DM and DN in Han population of Shanghai. The AER of people with GA+AA genotype is significantly higher than that with GG genotype. Arg913Gln (G→A) polymorphism of SLC12A3 gene may predict the risk of increase of albuminuria in patients with T2DM in Han population of Shanghai.