锌转运蛋白-8及转录因子7类似物-2基因多态性与中国南方汉族人2型糖尿病的相关性

Relationship of rs13266634 and rs11196218 polymorphisms in solute carrier family 30,member 8 and transcription factor 7 like-2 genes with type 2 diabetes in Han population in southern China

目的研究锌转运蛋白-8基因(SLC30A8)多态性位点rs13266634及转录因子7类似物-2基因(TCF7L2)多态性位点rs11196218与2型糖尿病(T2DM)以及相关代谢指标的关系。方法T2DM患者(T2DM组)259例,健康者(NC组)200名,均来自上海及周边地区。应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术判断标本基因型,同时进行人体测量学及代谢指标的检测,并分别采用稳态模型评估胰岛素抵抗指数(HOMA-IR)及胰岛B细胞分泌功能指数(HOMA-B)评估胰岛素抵抗和胰岛B细胞功能。结果①T2DM组中,rs13266634的C等位基因频率和CC基因型频率分别为57.3%和33.6%,均显著高于NC组的45.4%和17.2%(P值均<0.05)。②C等位基因携带者患T2DM的风险是T等位基因携带者的1.59倍(OR=1.59,95%CI为1.19～2.11,x^2=9.831,P=0.002)。与TT基因型相比,CC基因型患T2DM的风险增加2.63倍(OR=2.63,95%CI为1.42～4.87,x^2=9.69,P=0.002)。③T2DM组与NC组的TCF7L2(rs11196218)基因型及等位基因频率的差异均无统计学意义(P值均>0.05)。④T2DM组中,CC基因型的HOMA-B显著低于TT基因型(P=0.002)。结论SLC30A8基因rs13266634多态性位点的C等位基因可能是中国人T2DM的风险等位基因,而TCF7L2基因rs11196218单核苷酸多态性可能与T2DM的遗传易感性无关。

Objective To investigate the relationship of solute carrier family 30, member 8 gene （SLC30A8） and transcription factor 7 like-2 gene （TCF7L2） gene polymorphisms （rs13266634 for SLC30A8 and rs11196218 for TCF7L2） with type 2 diabetes mellitus and the relevant metabolic parameters. Methods A total of 259 patients with type 2 diabetes mellitus （T2DM group） and 200 normal controls （NC group） from Shanghai area were included in the present study. Polymorphisms of rs13266634 and rs11196218 were determined by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） assay with the genomic DNA. The genotype frequency was analyzed by Hardy-Weinberg disequilibrium. The metabolic parameters were measured and insulin resistance and B-cell functions were evaluated with HOMA-IR and HOMA-B methods. Results ①The frequencies of C allele and CC genotype of rs13266634 in T2DM group were 57.3% and 33.6%, respectively, which were significantly higher than those in NO group （45.4% and 17.2%, P〈0.05）. ②The risk of T2DM for those carrying C allele was 1.59 times higher than those carrying T allele （OR = 1.59, 95% CI： 1.19 - 2.11, χ^2 = 9.831, P = 0. 002）. As compared with the people with TT genotype, those with CO genotype showed a 2. 63-fold increase in risk of T2DM （OR=2.63, 95%CI： 1.42-4.87, χ^2 =9.69, P=0.002）. ② Analysis of metabolic parameters showed that those with C allele were associated with reduced secretion of insulin （the CC genotype compared with the TT genotype： P = 0. 002 ）. ③ In addition, there were no significant differences in the frequency of rs11196218 polymorphism between T2DM and NO groups. Conclusion These results indicate that C allele polymorphism of rs13266634 site in SLC30A8 gene might be a risk factor for T2DM, suggesting that SLC30A8 might be a susceptible gene for T2DM in the Han population in southern China, while the polymorphism of rsl 1196218 site in TCF7L2 gene may not be a risk factor for Chinese Han population.