摘要
目的 确定中国人胰岛素受体底物 - 1基因变异是否与 2型糖尿病相关。方法 用聚合酶链反应 -单链构象多态性分析方法筛选了 6 8例中国人 2型糖尿病患者和 6 8例正常对照组的胰岛素受体底物 - 1基因的 +170 0～ +4 437bp片段。再将单链构象多态性有改变的全部片段进行 DNA序列分析。结果 发现 2种出现氨基酸变化的核苷酸变异[GGG→ AGG(G971 R)和 CCT→ TCT(P1 0 79S) ]和 3种无声变异 [GAT→ GAC(D42 2 D)、CCA→ CCC(P737P)和 GCA→ GCG(A80 4A) ],其中 CCA→CCC(P737P)和 CCT→ TCT(P1 0 79S) ]是首次报道。这 5种核苷酸变异均在 2型糖尿病患者中发现 ,而在正常对照组中只发现 GCA→ GCG(A80 4A)。中国人 2型糖尿病患者这 5种变异的发生频率远高于正常对照组(38.2 % vs7.4% ,χ2 =18.42 ,P<0 .0 1)。最常见的多态性是 GCA→GCG(A80 4A) ,在 2型糖尿病患者中它的发生率远高于正常对照组 (2 6 .5 % vs7.4% ,2 =8.84,P <0 .0 1)。在 2型糖尿病患者和正常对照组中 ,该变异的纯合子发生率分别为 8.8%和 1.5 % (χ2 =2 .41,P >0 .0 5 )。结论 胰岛素受体底物 - 1基因的核苷酸变异可能与中国人 2型糖尿病的发生有相关性。
Objective To identify whether the mutation of insulin receptor substrate 1 (IRS 1) gene is associated with type 2 diabetes mellitus in Chinese. Methods The +1700～+4437 bp fragment of IRS 1 gene were screened using polymerase chain reaction (PCR) single strand conformation polymorphism (SSCP) analysis in 68 Chinese patients with type 2 DM and 68 control subjects. All SSCP variations were submitted to DNA sequence analysis.Results Two amino acid variations[GGG→AGG(G 971 R) and CCT→TCT(P 1079 S)] and 3 silent mutation [GAT→GAC(D 422 D), CCA→CCC(P 737 P) and GCA→GCG(A 804 A)] were identified, among which the CCA→CCC(P 737 P) and CCT→TCT(P 1079 S) have not previously been reported. All the five variations were found in Chinese patients with type 2 DM, while GCA→GCG(A 804 A) was the only one that was found in control subjects. The total incidence of the five variations in Chinese patients with type 2 DM were much higher than that in control subjects (38 2% vs 7 4%,χ 2=18 42, P<0 01). The most common polymorphism was GCA→GCG(A 804 A) in Chinese population, and its frequency was significantly higher in patients with type 2 DM than that in control subjects (26 5% vs 7 4%, χ 2=8 84,P<0 01). The homozygotes of the variation in patients with type 2 DM and control subjects were 8 8% and 1 5%, respectively (χ 2=2 41,P>0 05).Conclusion These results indicate that there may be a relation between these nucleotide variations of IRS 1 gene and Chinese type 2 DM.
出处
《中国糖尿病杂志》
CAS
CSCD
2000年第2期75-77,108,共4页
Chinese Journal of Diabetes
基金
国家自然科学基金
