内皮细胞固有型一氧化氮合酶基因内含子4插入/缺失多态性与糖尿病肾病的关系

Study on the association between ecNOS4b/a polymorphism and diabetic nephropathy

目的 对天津地区汉族人内皮细胞固有型一氧化氮合酶(ecNOS)基因内含子4的插入/缺失多态性(ecNOS4b/a)与2型糖尿病肾病(DN)的关联性进行研究。方法 应用PCR-小卫星DNA多态性分析技术对ecNOS4b/a基因型分布进行检测。包括正常对照组70例,2型糖尿病无DN组48例,2型糖尿病有DN无慢性肾功能不全(CRF)组35例,2型糖尿病DN有CRF组45例和非DN导致的CRF组58例。结果 (1)发现1例罕见基因型(女性DN无CRF患者),为447 bp+420 bp杂合子。(2)2型糖尿病无DN组a等位基因频率高于正常对照组,差异无显著性意义(x2=1.672,P=0.196)。(3)2型糖尿病伴DN组a等位基因频率低于2型糖尿病无DN组,差异无显著性意义(x2=1.082,P=0.298)。(4)DN无CRF组与DN伴CRF组等位基因频率相近(校正x2=0.002,P=0.967)。(5)DN伴CRF组a等位基因频率低于其它原因导致的CRF组,差异有显著性意义(x2=4.360,P=06037)。结论 a等位基因可能不是天津汉族人DN的危险因素;天津地区汉族健康人群a等位基因频率低于日本人;ecNOS在DN导致的CRF中的作用可能与非DN CRF不同。

Objective To examine the association between the insertion/deletion polymorphism in intron 4 of ecNOS gene (ecNOS4b/a) and diabetic nephropathy (DN) in the Han people of Tianjin, China. Methods The genotypes of ecNOS4b/a polymorphism were detected by PCR-minisatellite DNA detection technique. 70 healthy volunteers, 48 patients with type 2 diabetes without DN, 35 patients with type 2 diabetes and DN without chronic renal failure (CRF), 45 patients with DN in type 2 diabetes with CRF, and 58 patients with non-DN CRF were investigated. Results (1) One case (a female DN patient without CRF) with a rare genotype, the heterozygote of 447 bp and 420 bp, was found. (2) The frequency of allele a in type 2 diabetes without DN group was higher than that in control nonsignificantly (x2 = 1. 672, P = 0. 196) . (3) The frequency of allele a in DN group was lower than that in type 2 diabetes without DN group nonsignificantly (x2 = 1. 082, P = 0. 298). (4) The allele frequencies were similar between the DN without CRF group and the DN with CRF group (Continuity correction x2 = 0. 002, P = 0. 967). (5) The frequency of allele a in DN with CRF group was lower than that in non-DN CRF group significantly (x2=4. 360, P = 0. 037). Conclusions (1) Allele a is not a risk factor of DN in the Han people of Tianjin; (2) The frequency of allele a is lower in the Han people of Tianjin than that in Japanese(4. 3% vs 10. 1% , x2 = 4. 898, P = 0. 027); (3)There are different roles of ecNOS in DN-induced CRF and non-DN CRF.