维生素D受体基因BsmI多态性与2型糖尿病肾病的关系

目的 研究维生素D受体(VDR)基因BsmI位点多态性与汉族人群2型糖尿病肾病(DN)的关系.方法 应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测304例2型糖尿病患者(DM组)及100例健康体检者(NC组)VDR Bsml位点基因型和等位基因频率.根据尿白蛋白情况将DM组分为非糖尿病肾病组(DN0组,122例)、微量白蛋白尿组(DN1组,87例)、大量白蛋白尿组(DN2组,95例).83例病程5年以上仍未出现肾病的DM患者纳入L-NDN组；64例起病1年内即出现肾病的DM患者纳入EDN组.结果 DM组BB+Bb基因型和B等位基因频率均高于NC组(x2=7.088,P=0.008；x2=5.865,P=0.015).DN2组BB+Bb基因型和B等位基因频率高于NC组(x2=14.287,P=0.000; x2=12.621,P=0.000)及DN0组(x2=8.063,P=0.005;x2=8.173,P=0.004).其余组间差异均无统计学意义.EDN组BB+Bb基因型和B等位基因频率均显著高于L-NDN组(x2=7.228,P=0.007;x2=5.853,P=0.016).B等位基因阳性DN患者的尿白蛋白排泄率显著高于B等位基因阴性DN患者,差异有统计学意义(P＜0.01).BsmI位点基因型与DN发生密切相关.B等位基因阳性是DN发生及早发的危险因素(OR=2.004;0R=2.394).结论 VDRBsmI基因多态性与DN易感性相关.B等位基因阳性患者更易出现大量白蛋白尿及早期发生肾病.

Association of vitamin D receptor gene BsmI polymorphisms with type 2 diabetic nephropathy

Objective To investigate the association between BsmI polymorphism in vitamin D receptor (VDR) gene and diabetic nephropathy in Chinese Han population. Methods PCR-restriction fragment length polymorphism (PCR-RFLP) was used to test the genotype and allele frequency of BsmI in 304 patients with type 2 diabetes mellitus (DM group) and 100 healthy individuals (NC group). The DM group was further divided into non-diabetic nephropathy group (DN0 group, 122 cases), minimal albuminuria group (DN1 group, 87 cases), and mass albuminuria group (DN2 group, 95 cases). Eighty-three DM patients without nephropathy for over 5 years were L-NDN subgroup, and 64 DM patients with nephropathy occurring within the first year were EDN subgroup. Results Genotype and allele frequency of BsmI polymorphism were significantly different between DM and NC group (χ2=7.088, P=0.008; χ2=5.865, P=0.015). BB+Bb genotype and B allele frequency were significantly higher in DN2 group than those in NC group (χ2=14.287, P=0.000; χ2=12.621, P=0.000) and DN0 group (χ2=8.063, P=0.005; χ2=8.173, P=0.004). BB+Bb genotype and B allele frequency were significantly higher in EDN group than those in L-NDN group (χ2=7.228, P=0.007; χ2=5.853, P=0.016). DN patients with allele B (BB and Bb genotypes) presented higher urinary albumin excretion rates compared with patients without allele B (bb genotype, P＜0.01). The genotype of BsmI was correlated with DN, and allele B was risk factor of DN occurrence and early onset (OR=2.004; OR=2.394). Conclusion VDR gene BsmI polymorphism is associated with DN, and the patients carrying allele B are more involved in mass albuminuria and early onset of nephropathy.