Body mass index is an important determinant of methylation biomarkers in women of reproductive ages

B vitamin deficiencies lead to moderate hyperhomocysteinemia, which has been associated with health and disease. However, concomitant derangements in cellular methylation, reflected by altered plasma S-adenosylmethionine (SAM) or S-adenosylhomocysteine (SAH) concentrations, may be the primary cause. Therefore, we identified determinants of homocysteine, SAM, and SAH concentrations in 336 women, aged 20-48 y, as part of a large study focusing on risk factors for reproductive disorders. Blood was obtained to determine plasma SAM, SAH, and total homocysteine (tHcy), serum vitamin B-12 and folate, RBC folate concentrations, and the related single nucleotide polymorphisms 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C . T and 1298A . C, methionine synthase reductase (MTRR) 66A . G, and nicotinamide N-methyltransferase IVS1-151G . A. Questionnaires provided information on demographics, lifestyles, and nutrient intakes. Correlation coefficients were calculated and multivariable associations were assessed with a general linear model. Serum folate was positively correlated with SAM concentrations (r = 0.159; P = 0.004). Folate and vitamin B-12 were not correlated with SAH concentrations or the SAM:SAH ratio but were inversely correlated with tHcy concentrations (serum folate r = 20.324; RBC folate r = 20.294; vitamin B-12 r = 20.307; P , 0.01). From the multivariable analysis, BMI was the strongest determinant of SAM (standardized b = 19.145; P , 0.001) and SAH concentrations (standardized b = 3.241; P = 0.010). MTHFR 677TT (standardized b = 0.195; P = 0.001), B vitamin supplement use (standardized b = 20.156; P , 0.001) and dietary protein intake (standardized b = 20.011; P , 0.001) were the strongest determinants of tHcy concentrations. Thus, the determinants of SAM and SAH differ from those of tHcy concentrations. Given that BMI was a strong determinant of SAM concentrations, it should be included in future studies on cellular methylation.

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