Association of BHMT (rs 3733890) gene polymorphism with biochemical markers of B12 deficiency in T2DM patients on metformin therapy

Abstract

Long term administration of metformin interferes with the absorption of vitamin B12 resulting in vitamin B12 deficiency. Among the various genetic variants that are associated with vitamin B12 deficiency, we analyzed BHMT gene polymorphism and its association with metformin-induced vitamin B12 deficiency in T2DM patients. A cross-sectional study was conducted with 300 participants. Methylmalonic acid, homocysteine, and high-sensitivity C-reactive protein were analyzed by Mass Spectrometry, Chemiluminescent analyzer, and Immunoturbidimetric method, respectively. Genetic variants were analyzed by the ARMS-PCR method. Data were analyzed using various statistical tools like ROC, Odds ratio, and Likelihood ratio. Significant reduction in folic acid and vitamin B12 levels in metformin users was found. High sensitivity C-reactive protein, homocysteine, and methylmalonic acid were significantly increased in patients with metformin-induced B12 deficiency. The 'A' allele in BHMT (A allele OR = 2.1, AA genotype = 2.8) showed a risk of vitamin B12 deficiency in T2DM patients on metformin therapy. BHMT gene polymorphism had LR of 2.65 for folic acid (AG genotype), 2.73 for MMA (AA genotype), and 2.63 for Homocysteine (AA genotype). We found an association between single nucleotide polymorphism of BHMT and the diagnosis of vitamin B12 deficiency status in metformin users. Folic acid, MMA, and homocysteine had high specificity in concordance with BHMT (rs3733890) polymorphism in predicting vitamin B12 deficiency. Early screening of SNP of BHMT in T2DM patients on metformin therapy will help us to identify a group of people who are prone to vitamin B12 deficiency.