Interactions between genetic variants of folate metabolism genes and lifestyle affect plasma homocysteine concentrations in the Boston Puerto Rican population

Abstract

Objective: To investigate genetic and lifestyle factors and their interactions on plasma homocysteine (Hcy) concentrations in the Boston Puerto Rican population.

Design: Cross-sectional study. Plasma concentrations of Hcy, folate, vitamin B12 and pyridoxal phosphate were measured, and genetic polymorphisms were determined. Data on lifestyle factors were collected in interviews.

Setting: A population survey of health and nutritional measures.

Subjects: A total of 994 Puerto Rican men and women residing in the Boston metropolitan area.

Results: Smoking status was positively associated with plasma Hcy. Genetic polymorphisms MTHFR 677C→T, FOLH1 1561C→T, FOLH1 rs647370 and PCFT 928A→G interacted significantly with smoking for Hcy. MTHFR 1298A→C (P = 0·040) and PCFT 928A→G (P = 0·002) displayed significant interactions with alcohol intake in determining plasma Hcy. Subjects with PCFT 928GG genotype had significantly higher plasma Hcy concentrations compared with carriers of the A allele (AA+AG; P = 0·030) among non-drinking subjects. When consuming alcohol, GG subjects had lower plasma Hcy levels compared with AA+AG subjects. Physical activity interacted significantly with MTR 2756A→G in determining plasma Hcy (P for interaction = 0·002). Smoking interacted with physical activity for plasma Hcy (P for interaction = 0·023).

Conclusions: Smoking and drinking were associated plasma Hcy concentrations. Genetic variants involved in folate metabolism further modify the effects of lifestyle on plasma Hcy.

Conflict of interest statement

The authors report no conflict of interest.

Figures

Fig. 1

Effect of the interaction between drinking status and PCFT (proton-coupled folate transporter) genotype (PCFT 928G→A: ■, GG; □, AG+AA) on plasma homocysteine (Hcy) among men and women in the Boston Puerto Rican Health Study. Values are means with their standard deviations represented by vertical bars for the number of subjects given. Former drinkers and never drinkers were combined for comparison of plasma Hcy with current drinkers. Results were adjusted for age, sex, BMI, population admixture, smoking, energy intake, plasma folate, plasma vitamin B12, plasma pyridoxal phosphate, MTHFR 1298A→C and MTHFR 677C→T

Fig. 2

Effect of the interaction between physical activity and MTR (methionine synthase) genotype (MTR 2756A→G: ■, AA; □, AG+GG) on plasma homocysteine (Hcy) among men and women in the Boston Puerto Rican Health Study. Values are means with their standard deviations represented by vertical bars for the number of subjects given. Minor allele carriers (AG+GG) were compared with homozygous subjects (AA) under three categories of physical activity score (PA score) for plasma Hcy. Results were adjusted for age, sex, BMI, population admixture, smoking, drinking, energy intake, plasma folate, plasma vitamin B12, plasma pyridoxal phosphate, MTHFR 1298A→C and MTHFR 677C→T

Fig. 3

Effect of the interaction between physical activity and smoking status (■, non-smokers; □, smokers) on plasma homocysteine (Hcy) level among men and women in the Boston Puerto Rican Health Study. Values are means with their standard deviations represented by vertical bars for the number of subjects given. Non-smokers were compared with smokers under three categories of physical activity score (PA score) for plasma Hcy. Results were adjusted for age, sex, BMI, population admixture, drinking, energy intake, plasma folate, plasma vitamin B12, plasma pyridoxal phosphate, MTHFR 1298A→C and MTHFR 677C→T