HNF1A基因多态性及基因-环境交互作用与维吾尔族2型糖尿病关联性研究

The relationship between HNF1A gene polymorphisms,gene-environmental interaction and type 2 diabetes mellitus in the Uyghur population

目的探讨肝细胞核因子1A(HNF1A)基因单核苷酸多态性(SNP)位点rs2464196,rs1169288和rs1169289与维吾尔族T2DM的相关性,以及SNP-环境危险因素交互用对T2DM易感性的影响。方法在乌鲁木齐市选取156例T2DM患者(T2DM组)和248名健康人(NC组),进行基因多态性检测和交互作用分析。结果 rs2464196位点AG基因型和吸烟的交互作用与T2DM的风险相关(OR=2.284,P=0.041)。rs2464196位点AG基因型和高LDL-C水平的交互作用会增加T2DM风险(OR=4.157,P=0.005),rs2464196位点GG基因型与高TG、低HDL-C和高LDL-C交互作用增加维吾尔族T2DM的易感性(OR=2.908、3.058、5.619)。rs1169288位点TG基因型与高TC、高TG、低HDL-C和高LDL-C交互作用增加维吾尔族T2DM的易感性(OR=2.793、4.076、5.043、4.649)。GG基因型与高TG、低HDL-C和高LDL-C存在交互增加疾病易感性(OR=2.461、3.042、3.638)。rs1169289位点CG基因型与吸烟和高LDL-C存在交互(OR=5.370、4.575)。GG基因型与高TC、高TG、低HDL-C和高LDL-C有交互增加T2DM易感性(OR=2.250、2.170、2.999、4.217)。结论 HNF1A基因多态性rs2464196,rs1169288和rs1169289与吸烟、血脂异常的交互作用可能影响维吾尔族T2DM的易感性。

Objective To investigate the relationship between the common variations （rs2464196, rs1169288,and rs1169289） of HNFIA gene,gene-environmental interactions and type 2 diabetes （T2DM） in a Uyghur population. Methods A total of 156 patients with T2DM （T2DM group） and 248 normal controls （control group） were enrolled in this study. Gene polymorphisms were tested in all the subjects. The relationship between HNF1A variants and the risk of T2DM was assessed. Results For rs2464196, subjects with AG genotype who smoked or had a high LDL-C level got an increased risk of T2DM （OR= 2. 284,P=0. 041 and OR= 4. 157, P= 0. 005 respectively）. In conjunction with the GG genotype of this variant, higher TG,LDL-C, and lower HDL-C were associated with increased risk of T2DM （OR= 2. 908, 3. 058 and 5. 619）. For rs1169288, TG genotype with higher TC, TG, LDL-C and lower HDL-C was associated with increased risk for T2DM （OR = 2. 793, OR= 4. 076,5. 043 and 4. 649）. Meanwhile, those with GG genotype and higher TG, LDL-C, and lower HDL-C got increased risk for T2DM （OR= 2. 461,3. 042 and 3. 638）. For rs1169289, smoking or a high LDL-C in conjunction with the CG genotype was associated with increased risk for T2DM （OR=5. 370 and 4. 575）, while higher TC, TG, LDL C, and lower HDL C with CK3 genotype was associated with increased risk of T2DM （OR = 2. 250,2. 170,2. 999, and 4. 217）. Conclusion The HNF1A variants of rs2464196, rs1169288 and rs1169289 may interact with smoking and/or blood lipids and influence the risk of T2DM in the Uyghur population.