Diabetes, Metabolic Syndrome and Obesity (Jan 2021)
Association Between CDKAL1, HHEX, CDKN2A/2B and IGF2BP2 Gene Polymorphisms and Susceptibility to Type 2 Diabetes in Uttarakhand, India
Abstract
Amit K Verma,1,* Yamini Goyal,1,* Deepti Bhatt,1,* Mirza Masroor Ali Beg,2,* Kapil Dev,1 Mohammed A Alsahli,3 Arshad Husain Rahmani3 1Department of Biotechnology, Jamia Millia Islamia, New Delhi, India; 2Department of Biochemistry, Maulana Azad Medical College, New Delhi, India; 3Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia*These authors contributed equally to this workCorrespondence: Amit K VermaDepartment of Biotechnology, Srinivasa Ramanujan Block, Mujeeb Bagh, Jamia Millia Islamia, Lab 413, Medical Biotechnology Lab, 4 th Floor, New Delhi 110025, IndiaTel +91-9027777719Email [email protected]: 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.Keywords: type 2 diabetes, CDKAL1, CDKN2A/2B, IGF2BP2, HHEX, RFLP
