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Title: MAT1A variants modulate the effect of dietary fatty acids on plasma homocysteine concentrations and DNA damage

Author
item Huang, Tao - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY
item Tucker, Katherine - TUFTS UNIVERSITY
item Lee, Yu-chi - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY
item Crott, Jimmy - 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 - TUFTS UNIVERSITY
item Li, Duo - ZHEIJIANG UNIVERSITY
item Lai, Chao Qiang

Submitted to: Nutrition, Metabolism and Cardiovascular Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/27/2010
Publication Date: 12/23/2010
Citation: Huang, T., Tucker, K., Lee, Y., Crott, J., Parnell, L.D., Shen, J., Smith, C.E., Ordovas, J.M., Li, D., Lai, C. 2010. MAT1A variants modulate the effect of dietary fatty acids on plasma homocysteine concentrations and DNA damage. Nutrition, Metabolism and Cardiovascular Diseases. DOI: 1016/j.numecd.2010.07.015.

Interpretive Summary: Omega-3 poly-unsaturated fat (PUFA) from the diet shows a direct relationship with blood levels of homocysteine (Hcy), an important biomarker for cardiovascular disease. Methionine adenosyltransferase (MAT1A) is a key enzyme in biochemical pathway involving Hcy. The purpose of this study was to investigate the independent effect of dietary omega-3 fatty acids and genetic variants of the MAT1A gene on blood levels of Hcy among Boston Puerto Ricans. Plasma Hcy, levels of damage to DNA and MAT1A genetic variation were determined in 994 subjects, while data on dietary fatty acid intakes were collected in interviews concerning regular eating habits. Our results suggest that MAT1A genetic variants appear to modulate effects of dietary fat on plasma Hcy and DNA damage. This information is valuable for developing means to minimize certain cardiovascular disease.

Technical Abstract: Dietary n-3 polyunsaturated fatty acids (PUFA) are associated with decreased plasma homocysteine (Hcy), an important biomarker for cardiovascular disease. Methionine adenosyltransferase (MAT1A) is an enzyme involved in formation of form S-adenosylmethionine during methionine metabolism. The objective of this study was to investigate the independent effect of dietary fatty acids and MAT1A genotypes or their interaction on plasma Hcy concentrations among Boston Puerto Ricans. Plasma Hcy, DNA damage and MAT1A genotypes were determined in 994 subjects. Data on dietary fatty acid intakes were collected in interviews. Genetic variant MAT1A 3U1510 displayed significant interaction with dietary n-3:n-6 ratio in determining plasma Hcy (p=0.025). G homozygotes had significantly lower plasma Hcy concentration than major allele homozygotes and heterozygotes (AA+AG) (p=0.019) when the n-3:n-6 ratio was >0.09. Two other MAT1A variants also showed significant interaction with different constituents of dietary fat influencing Hcy concentration. In addition, MAT1A 3U1510 interacted with total PUFA (p=0.039) and total MUFA (p=0.046) on urinary 8-OHdG concentration, a biomarker of DNA damage. Our results suggest that MAT1A genotypes appear to modulate effects of dietary fat on plasma Hcy and DNA damage.