Preproghrelin基因Leu72Met多态性与T2DM和DN的关系

Relationship between Leu72Met polymorphism of Preproghrelin gene and type 2 diabetes mellitus and diabetic nephropathy

目的探讨前促生长激素释放多肽原(Preproghrelin)基因Leu72Met多态性(C→A)与2型糖尿病(T2DM)及糖尿病肾病(DN)的关系。方法以上海地区汉族人群中的252例T2DM患者(T2DM组)和83名口服葡萄糖耐量试验(OGTT)正常的非糖尿病非肾病对照者(对照组)作为研究对象。根据尿白蛋白排泄率(AER),将T2DM患者分为三组:未合并DN组(DN0组,n=92),合并DN微量蛋白尿组(DN1组,n=91)和合并DN大量蛋白尿组(DN2组,n=69)。采用PCR-RFLP法,检测各组Pre-proghrelin基因外显子2的Leu72Met多态基因型,比较组间基因型、等位基因频率分布及临床变量间的差异。结果T2DM组与对照组Preproghrelin基因型频率分布符合Hardy-Weinberg平衡,两组间Leu72Met多态基因型(CC、CA、AA)频率及等位基因(C、A)频率比较均无显著差异(P>0.05)。DN0、DN1、DN2组间比较,CA+AA基因型及A等位基因频率虽无显著差异,但依DN0组、DN1组、DN2组顺序呈下降趋势(基因型频率:44.5%vs38.5%vs36.2%;A等位基因频率:24.5%vs19.8%vs18.1%)。根据基因型分组进行临床变量比较表明,AA基因型组的AER显著低于CA与CC基因型组(P=0.035,P=0.019);血清肌酐水平及24 h尿蛋白定量依CC、CA、AA基因型顺序呈下降趋势(P>0.05)。结论上海地区汉族人群中,Preproghrelin基因Leu72Met多态性与T2DM及DN无显著相关性,但AA基因型携带者的尿微量白蛋白较CA和AA基因型携带者显著下降。推测Leu72Met多态性(C→A)可能具有延缓T2DM微量蛋白尿继续加重的作用。

Objective To explore the relationship between Leu72Met polymorphism （C→A） of Preproghrelin gene and type 2 diabetes mellitus （T2DM） and diabetic nephropathy （DN）. Methods Two hundred and fifty-two Shanghai Han ethnic people with T2DM （ T2DM group） and 83 non-DM controls with normal OGTT findings （ control group） were enrolled. According to albuminuric excretion rate （AER） , T2DM subjects were subdivided into non-DN group （ DN0 group, n =92） , microalbuminuria group （ DN1 group, n = 91 ） and macroalbuminuria group （ DN2 group, n = 69）. PCR-RFLP was employed to detect genotypes of Leu72Met polymorphism in exon 2 of Preproghrelin gene, genotypic and allelic frequencies and clinical characteristics were compared. Results There was no significant difference in genotypic （CC, CA, AA） or allelic （C, A）frequencies between T2DM group and control group （P 〉 0.05）. There was no significant difference in genotypic or allelic frequencies among DN0, DN1 and DN2 groups. However, declining tendency in CA ＋ AA genotypic and A allelic frequencies was observed in the order of DN0, DN1 and DN2 groups. T2DM with AA genotype had decreased AER when compared with CA and CC genotypes （P = 0. 035 and P =0. 019, respectively）. Serum creatinine and 24 h urinary protein were decreased in the order of CC, CA and AA genotypes（P 〉 0.05）. Conclusion Preproghrelin- Leu72Met is not significantly associated with T2DM and DN in Shanghai Han populations, while T2DM with AA genotype is characterized by significant declination in urine microalbumin when compared with CA and CC genotypes. Leu72Met polymorphism（C→A） may postpone the development of microalhuminuria in T2DM subjects.