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,
