神经源分化因子基因多态性与2型糖尿病的关联性研究

Association of polymorphism in neurogenic differentiation factor 1 gene with type 2 diabetes

目的 探讨神经源分化因子 (neurogenic differentiation factor 1,Neuro D)基因多态性与 2型糖尿病发生的关联性。方法 运用错配聚合酶链反应 -限制性片段长度多态性方法检测了中国湖北地区汉族 32 4例 2型糖尿病 (其中以发病年龄 40岁为界 ,分为早发及晚发两组 )及 12 4名正常对照者 ,Neuro D基因第 45位密码子碱基变异 (GCC→ ACC)。结果 Neuro D基因在所测人群中未发现有纯合变异者。在早发 2型糖尿病组 ,其 AT基因型频率为 2 6 .8% ,与正常对照组 (10 .5 % )及晚发 2型糖尿病组 (11.6 % )比较 ,差异有显著性 (分别为χ2 =7.85 ,P=0 .0 0 5 ;χ2 =8.81,P=0 .0 0 3) ;Thr45等位基因频率在早发 2型糖尿病组及正常对照组、晚发 2型糖尿病组分别为 13.4%、5 .2 %和 5 .8% ,差异亦有显著性 (χ2 =7.15 ,P=0 .0 0 8;χ2 =8.13,P=0 .0 0 4) ;晚发 2型糖尿病组与正常对照组比较 ,Ala45 Thr基因型频率 (11.6 % vs10 .5 % ,P>0 .0 5 )及等位基因频率 (5 .8% vs 5 .2 % ,P>0 .0 5 )差异不明显 ,Thr45等位基因与早发 2型糖尿病发生相关 (OR=2 .5 2 ,95 % CI:1.42～ 4.49) ;基因型为 AT型的 2型糖尿病患者其空腹血浆 C肽水平较 AA型患者低 ,差异有显著性 (P<0 .0 5 )。结论 Neuro D基因多态性与早发

Objective To evaluate the role of polymorphism in the neurogenic differentiation factor 1(NeuroD) gene in Chinese patients with type 2 diabetes mellitus. Methods The genotypes of codon 45 variant (GCC→ACC) in the Neuro D gene were determined by mismatch PCR-restriction fragment length polymorphism assay in 448 Chinese, including 124 subjects with normal glucose tolerance and 324 patients with type 2 diabetes mellitus. The diabetic patients were divided into two groups cutting off with the age of 40 at onset. Results No homozygote of the Ala45Thr variant was found in these subjects. The frequencies of AT heterozygous type were significantly higher in early-onset type 2 diabetic group than those in the control group and in the late-onset type 2 diabetic group (χ 2= 7.85, P = 0.005; χ 2=8.81, P = 0.003). The frequencies of Thr45 allele in the early-onset type 2 diabetic group were significantly different from those of the control group (13.4% vs 5.2%, χ 2=7.15, P =0.008) and the late-onset type 2 diabetic group (13.4% vs 5.8%, χ 2=8.13, P =0 004). The presence of Thr45 allele was shown to have an association with early-onset type 2 diabetes (OR=2.52,95% CI: 1.42- 4.49). Furthermore, the subjects carrying the variant appeared to have lower serum concentration of C-peptide in diabetic group. However, the frequencies of polymorphism genotypes of Neuro D gene showed no difference between the late-onset type 2 diabetic group and the control group. Conclusion The genetic polymorphism in the Neuro D is associated with the development of early-onset type 2 diabetes. The presence of Thr45 allele may represent a risk factor for early-onset type 2 diabetes among Chinese.