The Association of Methylenetetrahydrofolate Reductase C677T Polymorphism, Serum 5-Methyltetrahydrofolate, and Homocysteine Levels with Adenomyosis: A Cross-Sectional Study in an Indonesian Population

PURPOSE: Adenomyosis is a complex uterine condition, with emerging evidence indicating epigenetic alterations play a role in its pathogenesis. The methylenetetrahydrofolate reductase (MTHFR) gene polymorphism C677T may reduce enzyme activity, affecting DNA methylation and increasing adenomyosis risk. This study compares the MTHFR C677T polymorphism, 5-methyltetrahydrofolate (5-MTHF) levels, and homocysteine levels in patients with adenomyosis. PATIENTS AND METHODS: This cross-sectional study involved 61 subjects: 31 patients with adenomyosis and 30 patients as controls. The MTHFR C677T polymorphism was analyzed using PCR-RFLP, serum 5-MTHF and homocysteine levels were measured using ELISA. Statistical analyses were performed to compare genotype distributions and metabolite levels between groups and within the adenomyosis group based on genotype. RESULTS: The study found a significant difference in the distribution of the MTHFR C677T genotype between adenomyosis and control groups (p=0.018), with a higher prevalence of the CT genotype in the adenomyosis group (35.5% vs 10.0%). The frequency of the T allele was also elevated in the adenomyosis group (17.7% vs 5.0%; p=0.027). Serum 5-MTHF levels were notably lower in the adenomyosis group (23.92 ± 4.599 nmol/l) compared to controls (32.45 ± 3.019 nmol/l; p<0.0001), while homocysteine levels were significantly higher in the adenomyosis group (12.87 ± 8.916 µmol/L vs 8.61 ± 1.352 µmol/L; p=0.019). Further analysis of MTHFR genotypes indicated lower 5-MTHF levels in both CC and CT genotypes among the adenomyosis group compared to controls (p<0.0001). Homocysteine levels showed no significant difference across genotypes (p=0.074), though there was a trend towards higher levels in the adenomyosis group. CONCLUSION: This study demonstrates a significant difference in the distribution of the MTHFR C677T polymorphism, lower 5-MTHF levels, and higher homocysteine levels in patients with adenomyosis compared to controls. Lower 5-MTHF levels were also shown to be strongly linked with the heterozygous C677T polymorphism in the adenomyosis group.