中国全科医学2016，Vol.19Issue(10)：1170-1177,8.DOI:10.3969/j.issn.1007-9572.2016.10.014
细胞周期素依赖性蛋白激酶抑制因子2A/2B基因多态性与维吾尔族2型糖尿病的关系研究
Correlation Between Polymorphism of CDKN2A/2B Gene and Type 2 Diabetes Mellitus in Uygur People
摘要
Abstract
Objective To investigate the correlation between CDKN2A/ 2B gene and type 2 diabetes mellitus (T2DM)in Uygur people. Methods A total of 1 000 Uygur patients with T2DM who were hospitalized in the First Affiliated Hospital of Xinjiang Medical University from March 2012 to September 2013 were enrolled as T2DM group. In the same period, 1 010 Uygur people who received physical examination in the hospital and had no diabetes and no genetic connection among each other were enrolled as control group. All the subjects underwent physical examination and tests on biochemical indexes. Sequenom MassARRAY SNP was employed to detect the two loci susceptible to T2DM in CDKN2A/ 2B gene. SPSS 21. 0 statistical software was used for statistical analysis. We analysed genetic models,the interaction between genotype and BMI,and the interaction between haplotype and BMI using online software of SNPStats. Results Due to a small number of specimens that had unsuccessful gene loci detection,the total number of specimens detected with locus rs10811661 was 1 940(967 in control group and 973 in T2DM group),and that of specimen detected with locus rs564398 was 1 962(981 for both control group and T2DM group). There were statistical differences in the distribution of genotype and allele frequency of rs10811661 between T2DM group and control group(P < 0. 05),while there were no differences in the distribution of genotype and allele frequency of rs564398 (P > 0. 05). After adjustment for age,sex and BMI,the rs10811661 variants had significant differences between the two groups in co - dominant,dominant,over - dominant and additive models( P < 0. 05),while there were no differences in recessive model;the AIC and BIC of additive model were smallest,respectively being 2 602. 4 and 2 630. 3. The rs564398 variants had no differences between the two groups in each model(P > 0. 05). Compared with rs10811661 T/ T genotype with normal weight, T/ T and T/ C genotype with obesity had higher risk of T2DM,and the OR values were 2. 53〔95% CI(1. 80,3. 55)〕and 2. 17〔95% CI( 1. 50,3. 13 )〕 respectively( P < 0. 05 ) . Compared with rs564398 A/ A genotype with normal weight,A/ A genotype with overweight,and A/ A,A/ G and G/ G genotype with obesity had higher risk of type 2 diabetes mellitus,and the OR values were 1. 44〔95% CI(1. 03,2. 02)〕,2. 79〔95% CI(1. 99,3. 91)〕,2. 69〔95% CI(1. 86,3. 88)〕and 4. 81〔95% CI(2. 49,9. 29)〕respectively(P < 0. 05). The rs10811661 T/ T genotype with obesity had higher risk of T2DM than that with normal weight,with an OR value of 2. 53〔95% CI(1. 80,3. 55)〕 ( P < 0. 05),and T/ C genotype with overweight and obesity had higher risk of T2DM than that with normal weight,with OR values of 1. 56〔95% CI(1. 01,2. 40)〕and 3. 21〔95% CI(2. 09,4. 92)〕respectively(P < 0. 05). The rs564398 A/ A genotype with overweight and obesity,A/ G genotype with obesity,G/ G genotype with obesity had higher risk of T2DM than those with normal weight,and the OR values were 1. 44〔95% CI(1. 03,2. 02)〕,2. 79〔95% CI(1. 99,3. 91)〕,2. 09〔95% CI(1. 38,3. 15)〕and 5. 31〔95% CI (1. 68,16. 73)〕respectively(P < 0. 05). The rs10811661 C/ C genotype with obesity had lower risk of T2DM than that of rs10811661 T/ T genotype with obesity,and the OR value was 0. 48 〔 95% CI( 0. 27,0. 88 )〕( P < 0. 05 ) . Linkage disequilibrium analysis and haplotype building were conducted on 1 933 specimens that had successful detection of the two loci. After adjustment for age,sex and BMI,there was no strong linkage disequilibrium between rs10811661 and rs564398(D′= 0. 2682). CA haplotype had lower risk of T2DM than TA,with an OR value of 0. 78〔95% CI(0. 65,0. 94)〕(P < 0. 05). Obesity with TA,CA,CG and TG haplotype had higher risk of T2DM than normal weight with TA haplotype,and the OR values were 2. 94〔95% CI(1. 92,4. 50)〕,2. 14〔95% CI(1. 41,3. 25)〕,3. 05〔95% CI(1. 48,6. 28)〕and 3. 02〔95% CI (1. 98,4. 60)〕respectively(P < 0. 05). TA,CA,CG and TG haplotype with obesity had higher risk of T2DM than those with normal weight,and the OR values were 2. 94 〔95% CI( 1. 92,4. 50 )〕,2. 39 〔 95% CI( 1. 59,3. 59 )〕,3. 70〔95% CI(1. 11,12. 31)〕and 2. 59〔95% CI(1. 72,3. 90)〕 respectively( P < 0. 05). Obesity with CA haplotype had lower risk of T2DM than TA haplotype,with an OR value of 0. 73〔95% CI(0. 55,0. 97)〕(P < 0. 05). Conclusion The polymorphism of rs10811661 in CDKN2A/ 2B gene might be associated with the risk of T2DM in Uygur people,and this association might have interaction with BMI. Compared with C/ C genotype of rs10811661,the risk of T2DM with T/ T genotype increases,and T is the risk allele. The polymorphism of rs564398 in CDKN2A/ 2B gene has no association with the risk of T2DM in Uygur people. The CG haplotype of rs10811661 and rs564398 with obesity has the highest risk of type 2 diabetes mellitus.关键词
糖尿病,2型/细胞周期素依赖性蛋白激酶抑制因子2A/2B/维吾尔族/关系Key words
Diabetes mellitus,type 2/Cyclin - dependent kinase inhibitor 2A/ 2B/Uygur nationality/Relation分类
医药卫生引用本文复制引用
肖珊,曾小云,朱筠,姚华,苏银霞,马琦..细胞周期素依赖性蛋白激酶抑制因子2A/2B基因多态性与维吾尔族2型糖尿病的关系研究[J].中国全科医学,2016,19(10):1170-1177,8.基金项目
国家973科技项目（2012CB722403）---维吾尔族代谢综合征遗传差异及其与环境交互作用研究 （）
