MTHFR Polymorphisms and Their Association with Biochemical Risk Markers in Type 2 Diabetes Mellitus Complications

Abstract

Background: Type 2 Diabetes Mellitus (T2DM) is a multifactorial disease with a strong genetic component. The MTHFR C677T polymorphism (rs1801133) has been implicated in various complications associated with T2DM. The present study investigates the role of the MTHFR C677T polymorphism in T2DM patients from Kerala, India.

Methods: A cross-sectional study was conducted, involving 40 participants, consisting of 20 T2DM patients and 20 healthy controls. Genotyping of the MTHFR C677T polymorphism was performed using polymerase chain reaction (PCR) and quantitative PCR (qPCR). Sanger sequencing was employed for genotype confirmation. Biochemical parameters, including HbA1c, serum creatinine, and microalbuminuria, were measured using standard clinical assays. The data were analyzed for genotype-phenotype associations using non-parametric tests and Spearman’s correlation.

Results: The T allele of the C677T polymorphism was more prevalent in T2DM patients (37.5%) compared to healthy controls (20%). A significant association was found between the T allele and higher HbA1c levels (8.1% ± 1.6% in T2DM patients with CT/TT genotypes versus 7.6% ± 1.5% in CC genotype carriers, p = 0.12). Additionally, microalbuminuria levels were higher in T allele carriers (213.7 mg/L) compared to CC genotype carriers (31.0 mg/L), although this difference did not reach statistical significance (p = 0.09). Serum creatinine levels were also elevated in T allele carriers (1.40 mg/dL) compared to CC genotype carriers (0.85 mg/dL). Spearman’s correlation analysis revealed a moderate positive correlation between HbA1c and microalbuminuria (Rs = 0.76, p = 0.001), indicating that glycemic control is linked to early renal damage in T2DM.

Conclusion: Our study suggests that the MTHFR C677T polymorphism is associated with altered glycemic control and potential early renal complications in T2DM patients. Larger, longitudinal studies with homocysteine measurements and ethnically diverse cohorts are needed to validate these findings and better understand the role of MTHFR polymorphisms in T2DM progression.