印度北阿坎德邦CDKAL1、HHEX、CDKN2A/2B和IGF2BP2基因多态性与2型糖尿病易感性的关联
Association Between CDKAL1, HHEX, CDKN2A/2B and IGF2BP2 Gene Polymorphisms and Susceptibility to Type 2 Diabetes in Uttarakhand, India.
作者信息
Verma Amit K, Goyal Yamini, Bhatt Deepti, Beg Mirza Masroor Ali, Dev Kapil, Alsahli Mohammed A, Rahmani Arshad Husain
机构信息
Department of Biotechnology, Jamia Millia Islamia, New Delhi, India.
Department of Biochemistry, Maulana Azad Medical College, New Delhi, India.
出版信息
Diabetes Metab Syndr Obes. 2021 Jan 6;14:23-36. doi: 10.2147/DMSO.S284998. eCollection 2021.
INTRODUCTION
Current study aimed to find the association of genes polymorphism of CDKAL1, HHEX, CDKN2A/2B, and IGF2BP2 with type 2 diabetes (T2DM) in the population of Uttarakhand.
RESEARCH DESIGN AND METHODS
Overall 469 persons comprising 369 recently diagnosed T2DM cases and 100 healthy control were enrolled in the present study. The polymorphisms were analyzed through the PCR-RFLP technique.
RESULTS
For the rs10440833 variant (CDKAL1), CC genotype's frequency was significantly high among T2DM subjects than controls and increase the T2DM risk (OR: 4.46, 95% CI: 2.22-8.99, p <0.0001). The c allele was significantly found to increase the T2DM risk (OR: 2.20, 95% CI: 1.54-3.14, p <0.001). In the rs1111875 variant (HHEX), the difference of genotype frequencies among T2DM cases and control was statistically non-significant (p-0.138). We did not observe significant differences in allelic frequencies among T2DM cases and control (p-0.444). In the case of rs10811661 variant (CDKN2A/2B), frequency of both TC (OR: 3.16, 95% CI: 1.84-5.42, p <0.0001) and TT (OR: 5.84, 95% CI: 1.75-19.45, p -0.004) genotype were significantly higher in T2DM cases in comparison with control and significantly associated with higher T2DM risk. Compared to the C allele, a significant increase in T2DM risk was documented with the T allele (OR: 2.47, 95% CI: 1.55-3.92, p <0.001). For rs4402960 variant (IGF2BP2), TT genotype contributed to increased T2DM risk (OR: 4.25, 95% CI: 2.02-8.93, p -0.0001). T allele's frequency was significantly high in T2DM cases in comparison with healthy control. Except WHR, HDL-C, exercise, household chores, standing work more than 3 hours, and family history, significant differences were found between T2DM cases and healthy individuals in all other parameters.
CONCLUSION
Our study concluded a significant association of CDKAL1, CDKN2A/2B, and IGF2BP2 polymorphism with T2DM in the Uttarakhand population. For HHEX, the genotype and allelic frequencies difference between T2DM cases and control were statistically non-significant. However, a significant association of HHEX gene polymorphism with T2DM was observed only under the dominant model.
引言
当前研究旨在探寻在北阿坎德邦人群中，细胞周期蛋白依赖性激酶5调节亚基相关蛋白1（CDKAL1）、肝细胞核因子1β（HHEX）、细胞周期蛋白依赖性激酶抑制剂2A/2B（CDKN2A/2B）和胰岛素样生长因子2 mRNA结合蛋白2（IGF2BP2）的基因多态性与2型糖尿病（T2DM）之间的关联。
研究设计与方法
本研究共纳入469人，其中包括369例新诊断的T2DM患者和100名健康对照。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术分析基因多态性。
结果
对于rs10440833变异位点（CDKAL1），T2DM患者中CC基因型的频率显著高于对照组，且增加了T2DM风险（比值比：4.46，95%置信区间：2.22 - 8.99，p <0.0001）。显著发现c等位基因增加了T2DM风险（比值比：2.20，95%置信区间：1.54 - 3.14，p <0.001）。对于rs1111875变异位点（HHEX），T2DM患者与对照组之间基因型频率的差异无统计学意义（p = 0.138）。我们未观察到T2DM患者与对照组之间等位基因频率的显著差异（p = 0.444）。对于rs10811661变异位点（CDKN2A/2B），与对照组相比，T2DM患者中TC基因型（比值比：3.16，95%置信区间：1.84 - 5.42，p <0.0001）和TT基因型（比值比：5.84，95%置信区间：1.75 - 19.45，p = 0.004）的频率均显著更高，且与更高的T2DM风险显著相关。与C等位基因相比，T等位基因显著增加了T2DM风险（比值比：2.47，95%置信区间：1.55 - 3.92，p <0.001）。对于rs4402960变异位点（IGF2BP2），TT基因型增加了T2DM风险（比值比：4.25，95%置信区间：2.02 - 8.93，p = 0.0001）。与健康对照组相比，T2DM患者中T等位基因的频率显著更高。除腰臀比、高密度脂蛋白胆固醇、运动、家务劳动、站立工作超过3小时和家族史外，T2DM患者与健康个体在所有其他参数上均存在显著差异。
结论
我们的研究得出结论，在北阿坎德邦人群中，CDKAL1、CDKN2A/2B和IGF2BP2基因多态性与T2DM存在显著关联。对于HHEX，T2DM患者与对照组之间基因型和等位基因频率的差异无统计学意义。然而，仅在显性模型下观察到HHEX基因多态性与T2DM存在显著关联。
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