Role of DNA repair XRCC1 and XRCC3 gene polymorphisms in the predisposition to type 2 diabetes in Bangladesh

Abstract

This study explores the potential association between specific polymorphisms in the X-ray cross- complementing group 1 (XRCC1) gene (Arg194Trp, Arg280His, Arg399Gln) and X-ray cross- complementing group 3 (XRCC3) gene Thr241Met and the susceptibility to Type 2 Diabetes Mellitus (T2DM) in the Bangladeshi population. Recognizing the established links between hyperglycemia, oxidative stress, and DNA damage and the increased cancer risk in individuals with T2DM, our case-control investigation involved 150 T2DM patients and 150 controls with normal glucose metabolism in Dhaka, Bangladesh. Polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) was employed to assess the genotypic distribution and allele frequencies of XRCC1 and XRCC3 polymorphisms. The analysis revealed that XRCC1 194 (Arg/Trp), XRCC1 280 (Arg/His), and XRCC1 399 (Arg/Gln) variants were associated with 2.09, 2.36, and 2.04-fold higher risks of T2DM, respectively. The XRCC3 Thr241Met variant also demonstrated a 2.64-fold increased risk for T2DM in the Bangladeshi population. We observed a significantly high risk associated with gene-gene interaction in individuals possessing XRCC1 Arg280His-XRCC3 Thr241Met genotypes, indicating a considerably higher risk compared to that associated with those genotypes alone. No relation was found with T2DM and smoking status but found a significant positive association (p<0.001) of blood pressure with diabetes in diabetic subjects compared to control. However, the study acknowledges its limitations, such as a relatively small sample size emphasizing the need for further research to validate and expand upon these genetic associations