The MTHFR C677T/A1298C polymorphism is associated with increased risk of microangiopathy in type 2 diabetes mellitus: A systematic review and meta-analysis

Extensive case-control association studies have been conducted over the past few decades to investigate the relationship between MTHFR polymorphism and type 2 diabetes mellitus (T2DM) microangiopathy. However, the strength of the evidence and clinical significance are unclear. Consequently, a meta-analysis was performed to examine the correlations between two prevalent MTHFR single nucleotide polymorphisms, MTHFR C677T and A1298C, and T2DM microangiopathy. Randomized controlled trials were systematically searched in PubMed, Cochrane, Embase, Web of Science, CNKI, VIP database, China Biology Medicine, and Wanfang until August 2023. A total of 42 studies were included. Random-effect models were utilized to estimate odds ratios (ORs) with 95% confidence intervals (CIs) to assess the association between MTHFR polymorphisms and T2DM microangiopathy susceptibility. T2DM microangiopathy was significantly associated with the MTHFR C677T polymorphism in the overall population (T vs C, OR = 1.43, 95% CI = 1.25-1.64; TT + CT vs CC: OR = 1.56, 95% CI = 1.30-1.88; TT vs CT + CC: OR = 1.66, 95% CI = 1.38-1.99; TT vs CC: OR = 2.03, 95% CI = 1.58-2.60). Additionally, the dominant model revealed that the MTHFR A1298C polymorphism was associated with T2DM microangiopathy (OR = 1.27, 95% CI: 1.09-1.47). This meta-analysis revealed that MTHFR may be involved in the pathogenesis of T2DM microangiopathy, providing a reference for early diagnosis and treatment of T2DM.