中国人胰岛素受体基因EXON2-2257位点多态性与胰岛素抵抗的关系  

Study on the relationship between polymorphism of insulin-receptor gene EXON2-2257 and insulin resistance in Chinese people

作　　者：王璐[1] 米杰[2] 吴建新[3] 赵小元[3] 程红[2] 丁秀原[4] 侯冬青[2] 鲁杰[3] 顾雪[2] 

机构地区：[1]中国医学科学院基础医学研究所中国协和医科大学基础医学院流行病学教研室,北京100005 [2]首都儿科研究所流行病学研究室 [3]首都儿科研究所生化免疫研究室 [4]首都儿科研究所遗传研究室

出　　处：《中华流行病学杂志》2004年第1期49-53,共5页Chinese Journal of Epidemiology

基　　金：国家自然科学基金资助项目(39970658)

摘　　要：目的 从群体角度探讨胰岛素抵抗与胰岛素受体基因多态性的关系。方法 用聚合酶链反应(PCR)对某一特定队列中国人群的胰岛素受体基因第二外显子(EXON2)进行扩增,并用PCR产物直接测序法对EXON2进行了单核苷酸序列分析。结果 在EXON2-2257位点测得单核苷酸多态性,在345人中表现为:纯合CC基因型237人,占68.70％,基因频率0.825;纯合TT基因型13人,占3.77％,基因频率0.175;杂合CT基因型95人,占27.54％,符合Hardy-Weinburg平衡(X2=0.2898,u=3-2=1,0.5<P<0.75)。男女TT、CT基因型人群的甘油三酯水平、稳态模式评估法(HOMA)评价的胰岛素抵抗指数(HOMA-IR)均显著低于CC基因型人群(P<0.05);与CC基因型相比,C基因型在胰岛素抵抗组的构成比(18.4％)显著低于对照组(30.6％)(P=0.022,OR=0.493);TT基因型虽然在胰岛素抵抗组的构成比(2.3％)低于对照组(4.3％),但P=0.297,差异无显著性。logistic分析结果表明:在调整了诸如服用降压药、降糖药、血脂浓度、体重指数和高血压等因素的混杂作用后,与CC基因型人群相比,CT基因型人群患胰岛素抵抗的危险性OR=0.448,95％CI:0.214～0.940。结论 CT基因型可能是胰岛素抵抗的一个保护性基因型的候选基因。Objective To understand the role of insulin-receptor gene in the development of insulin resistance on a population-based study in China. Methods Polymerase chain reaction (PCR) was used to amplify the EXON2 of the insulin-receptor gene and all amplified products were analyzed by direct sequencing. Results Three genotypes of single nucleotide at the site of 2257 in EXON2 of the insulin-receptor gene were identified. In 237 of the 345 cases (68.7% ), homozygote genotype of CC phenotype was found with a gene frequency of 0.825; 13 cases (3.77%) showed homozygote genotype of TT phenotype with a gene frequency of 0.175 and the rest 95 cases (27.54%) showed heterozygote genotype of CT phenotype. Data were in agreement with the test of Hardy-Weinberg balance (X2 =0.2898,v=3-2= 1,0.5<P< 0.75). The serum level of triglyceride and the HOMA-IR index, the status of insulin resistance assessed by homeostasis model assessmend (HOMA), were lower in the TT or CT genotype group than that in the CC genotype group (P<0.05). Comparing with CC genotype, the proportion of CT genotype (18.4%) in the insulin resistance group (large than 75th percentile of HOMA-IR) was significantly lower than that in the control group (30.6%)(P = 0.022, OR = 0.493). The proportion of TT genotype (2.3%) in insulin resistance group was lower than that in the control group (4.3% , P = 0.297). logistic analysis revealed that after adjusting possible confounding factors such as taking anti-hypertensive and anti-diabetic medications, serum triglyceride and high density lipoprotein cholesterol (HDL-C), hypertension, BMI, smoking history, the OR value of people in the insulin resistance group with CT genotype was 0.448 (95% CI: 0.214 to 0.940) compared to the group with CC genotype. Conclusion The hybridization CT genotype at the site of 2257 in EXON2 of insulin-receptor gene might have a candidate gene to serve as a protective factor for insulin resistance.

关 键 词：中国人 胰岛素受体基因 EXON2-2257位点 多态性 胰岛素抵抗 

分 类 号：R587[医药卫生—内分泌]