Association between MTHFR C677T Gene Polymorphism and the Risk of Type 2 Diabetes Mellitus among Patients at the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia.

Abstract

Type 2 Diabetes Mellitus (T2DM) is a multifactorial metabolic disorder characterized by chronic hyperglycemia due to defects in insulin secretion, insulin action, or both. Both environmental and genetic factors contribute to its development. The Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, which affects folate metabolism and homocysteine levels, has been implicated in various metabolic disorders, including T2DM. However, its association with T2DM risk remains inconsistent across different populations, and its role in Ethiopian popula tions has been largely understudied. The objective of this study was to investigate the association Between MTHFR C677T gene polymorphism and the risk of Type 2 Diabetes Mellitus among patients at the University of Gondar Comprehensive Specialized Hospital. A comparative cross sectional study was conducted among 140 T2DM patients and 140 control individuals, selected using a non-randomized purposive sampling technique. Data collection included socio-demo graphic and lifestyle factors, clinical examination, and genetic analysis using PCR-RFLP to de tect the MTHFR C677T polymorphism. Statistical analyses were performed using chi-square tests, and bivariate and multivariate logistic regression. Results were expressed as odds ratios (OR) with 95% confidence intervals (CI), and a p-value < 0.05 was considered statistically sig nificant. The results showed that individuals aged 30-44 years (AOR = 2.50, p = 0.028) and 45 59 years (AOR = 2.28, p = 0.037) had significantly higher odds of T2DM compared to those aged 18-29 years. Other significant risk factors included elevated blood pressure (AOR = 1.97, p = 0.019), family history of diabetes (AOR = 2.12, p = 0.010), alcohol consumption (AOR = 1.82, p = 0.035), and smoking (AOR = 1.89, p = 0.037). Regarding BMI, underweight individuals showed a trend toward higher risk (AOR = 3.99, p = 0.056), though not statistically significant. Additionally, the MTHFR C677T polymorphism showed notable genetic associations, with the CT genotype (AOR = 5.00, p = 0.001) and TT genotype (AOR = 2.54, p = 0.050) increasing T2DM susceptibility compared to the CC genotype. While vegetable consumption and physical activity showed a trend toward association, they did not reach statistical significance. This result indicates that age, elevated blood pressure, family history of diabetes, alcohol consumption, smoking, and the MTHFR C677T are significant risk factors for T2DM. Further research with larger and more diverse populations is recommended to validate this result and explore the mech anisms behind the observed associations. Keywords: Genetic Association, Gene Polymorphism, MTHFR C677T,