MAT1A variants modulate the effect of dietary fatty acids on plasma homocysteine concentrations

Abstract

Background and aim: Dietary n-3 polyunsaturated fatty acids (PUFAs) are associated with decreased plasma homocysteine (Hcy), an important biomarker for cardiovascular disease. The S-adenosylmethionine synthetase type-1 (MAT1A), an essential enzyme in the conversion of methionine to S-adenosylmethionine, plays a key role in homocysteine metabolism. This study investigated the interaction between dietary fatty acids and MAT1A genotypes on plasma Hcy concentrations among Boston Puerto Ricans.

Methods and results: Plasma Hcy and MAT1A genotypes were determined in 994 subjects of the Boston Puerto Rican Health Study. Dietary fatty acid intakes were assessed by interviews using a questionnaire adapted from the NCI/Block food frequency form.

Result: In the cross-sectional analysis, genetic variant MAT1A 3U1510 displayed a significant interaction with dietary n-3:n-6 PUFA ratio in determining plasma Hcy (p-value for interaction = 0.025). 3U1510G homozygotes had significantly lower plasma Hcy concentration than major allele homozygotes and heterozygotes (AA + AG) (p-value for trend = 0.019) when the n-3:n-6 ratio was >0.09. Two other MAT1A variants, d18777 and i15752, also showed significant interactions with different constituents of dietary fat influencing Hcy concentrations. Furthermore, haplotypes consisting of three variants displayed a strong interaction with n3:n6 ratio influencing Hcy concentrations.

Conclusions: Our results suggest that MAT1A genotypes appear to modulate effects of dietary fat on plasma Hcy.

Conflict of interest statement

No potential conflicts of interest

Published by Elsevier B.V.

Figures

Figure 1

A. Interaction between dietary MUFA and MAT1A i15752 on plasma homocysteine. Adjusted for age, sex, BMI, population admixture, smoking, alcohol use, dietary energy, plasma folate, plasma vitamin B12 and plasma vitamin B6, and genotypes of MTHFR 1298 A>C and MTHFR 677 C>T. Sample size: GG (n=360); AG+AA (n=532) B. Interaction between dietary MUFA and MAT1A d18777 on plasma homocysteine: Adjusted for age, sex, BMI, population admixture, smoking, alcohol consumption, dietary energy, plasma folate, plasma vitamin B12 and plasma vitamin B6, and genotypes of MTHFR 1298 A>C and MTHFR 677 C>T. Sample size: GG (n=430); AG+AA(n=390).