title: Body mass index is an important determinant of methylation biomarkers in women of reproductive ages.
abstract: 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 = -0.324; RBC folate r = -0.294; vitamin B-12 r = -0.307; P < 0.01). From the multivariable analysis, BMI was the strongest determinant of SAM (standardized beta = 19.145; P < 0.001) and SAH concentrations (standardized beta = 3.241; P = 0.010). MTHFR 677TT (standardized beta = 0.195; P = 0.001), B vitamin supplement use (standardized beta = -0.156; P < 0.001) and dietary protein intake (standardized beta = -0.011; 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.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Obstetrics and Prenatal Medicine, Erasmus Medical Center, University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Lydi M J W
authors.initials: LM
authors.lastname: van Driel
authors.forename: Marinus J C
authors.initials: MJ
authors.lastname: Eijkemans
authors.forename: Robert
authors.initials: R
authors.lastname: de Jonge
authors.forename: Jeanne H M
authors.initials: JH
authors.lastname: de Vries
authors.forename: Joyce B J
authors.initials: JB
authors.lastname: van Meurs
authors.forename: Eric A P
authors.initials: EA
authors.lastname: Steegers
authors.forename: Régine P M
authors.initials: RP
authors.lastname: Steegers-Theunissen
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D015992:Body Mass Index; D005260:Female; D005298:Fertility / Q000502:physiology*; D005492:Folic Acid / Q000097:blood; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008019:Life Style; D008745:Methylation; D008875:Middle Aged; D015999:Multivariate Analysis; D009426:Netherlands; D012435:S-Adenosylhomocysteine / Q000097:blood; D012436:S-Adenosylmethionine / Q000097:blood*; D011795:Surveys and Questionnaires; D014805:Vitamin B 12 / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006710:Homocysteine; D012436:S-Adenosylmethionine; D005492:Folic Acid; D012435:S-Adenosylhomocysteine; D014805:Vitamin B 12