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

Author
item HUANG, TAO - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item TUCKER, KATHERINE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item LEE, YU-CHI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item CROTT, JIMMY - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item Parnell, Laurence
item SHEN, JIAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item SMITH, CAREN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item LI, DUO - Zhejiang University
item Lai, Chao Qiang

Submitted to: Molecular Nutrition and Food Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/20/2010
Publication Date: 2/22/2011
Citation: Huang, T., Tucker, K., Lee, Y., Crott, J., Parnell, L.D., Shen, J., Smith, C., Ordovas, J., Li, D., Lai, C. 2011. Interactions between genetic variants of methionine metabolism genes and lifestyle affect plasma homocysteine concentrations in the Boston Puerto Rican Population. Molecular Nutrition and Food Research. DOI: 10.1017/S1368980011000140.

Interpretive Summary: Elevated plasma homocysteine (Hcy) is known as an important risk factor for cardiovascular disease. Many studies that investigated the relationship between lifestyle factors, including diet and exercise, often do not agree. We hypothesize that genetic variants modulate the correlation between lifestyle and plasma Hcy. The aim of this study was to investigate the combined effect of genetic and lifestyle factors on plasma Hcy concentrations in a population of Boston Puerto Ricans. We observed that smoking tobacco was significantly associated with plasma levels of Hcy. Persons with a common version of a particular variant had significantly higher plasma Hcy concentrations compared to persons carrying one or two copies of the rarer variant. This was observed in subjects who reported no intake of alcohol. However, persons who had such a variant and reported consumption of alcohol had lower plasma Hcy concentrations. In other words, the combination of carrying a particular genetic variant and consumption of no alcohol associated with increased plasma Hcy, which has been linked to incidence of heart disease. In summary, our results showed that genetic variants modified the effect of lifestyle on plasma Hcy. These findings suggest that healthy lifestyle is particularly important to prevent CVD for a subset of population who carry a particular genetic variant. For instance, to lower Hcy for the prevention of CVD, carriers (66%) of a particular variant would benefit greatly from not smoking, whereas such subjects (34%) may gain benefit from consuming alcohol.

Technical Abstract: Results of studies investigating relationships between lifestyle factors and elevated plasma homocysteine (Hcy), an independent risk factor for cardiovascular disease, are conflicting. The objective of this study was to investigate genetic and lifestyle factors and their interactions on plasma Hcy concentrations in the Boston Puerto Rican Population. Plasma concentrations of Hcy, folate, vitamin B12, pyridoxal phosphate, and genetic polymorphisms were measured in 994 subjects. Data on lifestyle factors were collected in interviews. Smoking status was significantly associated with plasma Hcy. Genetic variants MTHFR 677 C>T, FOLH1 1561C>T, rs647370 FOLH1, 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. PCFT 928 GG subjects had significantly higher plasma Hcy concentrations when compared with homozygous minor and heterozygote subjects (AA+AG) (P=0.030) among non-drinking subjects. Furthermore, those GG subjects who consumed alcohol had a lower plasma Hcy level when compared with AA+AG subjects. Physical activity significantly interacted 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). Present results suggested that age, smoking and drinking influence plasma Hcy concentration. Genetic variants involved in folate metabolism further modify the effects of lifestyle on plasma Hcy.