Screening of Type 2 Diabetes Patients of Khyber Pakhtunkhwa for CDKAL1 Variant (rs10946398)

Diabetes Mellitus Type 2 (T2DM) is a metabolic disorder influenced by environmental and genetic factors, with varied genetic predispositions across populations. Research on T2DM's genetic risk factors in the Pakistani community is limited. Objective: To explore the association between the CDKAL1 gene variant (rs10946398) and T2DM in the Khyber Pakhtunkhwa population in Pakistan. Methods: The study involved 100 T2DM patients and 100 controls, matched by age and gender, following specific inclusion and exclusion criteria. Sociodemographic data were collected alongside 3ml of whole blood for DNA extraction. The CDKAL1 gene was analyzed using PCR-based Sequence Restriction Fragment Length Polymorphism (RFLP), and the data were processed with SPSS version 26.0s. Results: Findings showed that 47% of cases were aged 39 to 59, with 94% having a family history of T2DM and 85% leading a sedentary lifestyle. A significant association was observed between the CDKAL1 rs10946398 variant and T2DM. The GC variant was linked to a fourfold increase in risk (OR: 4.833, CI: 1.197-19.509, P=0.027), and the CC variant had a twofold association (OR: 2.788, CI: 1.545-5.033, P=0.001). These associations persisted after adjusting for family history, age, socioeconomic factors, exercise, and diet. Conclusions: The study identified a significant correlation between the CDKAL1 rs10946398 variants and T2DM susceptibility in the Khyber Pakhtunkhwa population, emphasizing the role of genetic factors in the disease's prevalence within this community.