Juan Juan1,2, Hongyan Huang2, Xia Jiang2, Andres V Ardisson Korat3,4, Mingyang Song3,5, Qi Sun3,6, Walter C Willett3,4,6, Majken K Jensen3,6, Peter Kraft2,4,7. 1. Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing, China. 2. Program in Genetic Epidemiology and Statistical Genetics. 3. Departments of Nutrition, Epidemiology, and Biostatistics, Harvard TH Chan School of Public Health, Boston, MA. 4. Departments of Epidemiology, and Biostatistics, Harvard TH Chan School of Public Health, Boston, MA. 5. Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA. 6. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. 7. Departments of Biostatistics, Harvard TH Chan School of Public Health, Boston, MA.
Abstract
Background: Polyunsaturated fatty acids (PUFAs) are associated with a lower risk of multiple diseases. Fatty acid desaturase 1 gene (FADS1) polymorphisms and dietary PUFA intake are both established determinants of circulating PUFA proportions. Objective: We explored the joint effects of FADS1 polymorphisms and dietary PUFA intake on circulating PUFA proportions. Design: We studied 2288 participants from a nested case-control study of coronary artery disease among participants who provided blood samples in the Nurses' Health Study and the Health Professionals Follow-Up Study. Dietary PUFA intake was obtained from semiquantitative food-frequency questionnaires. FADS1 rs174546 was genotyped by using the Affymetrix 6.0 platform, and circulating PUFA proportions were measured with gas-liquid chromatography. Linear regression models were used to examine the associations between rs174546 and circulating proportions of each fatty acid. Gene-diet interactions were tested by including a cross-product term of dietary intake of each PUFA by rs174546 genotype in the linear regression models. Results: After adjustment for sex and ancestry, each copy of the C allele of rs174546 was associated with higher circulating proportions of arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) and lower proportions of linoleic acid and α-linolenic acid. The magnitude of positive association between higher consumption of dietary EPA or DHA and circulating proportions of EPA increased with each copy of the rs174546_T allele (P-interaction = 0.01 and 0.007, respectively). Each 1-SD increment in EPA intake was associated with an average 3.7% increase in circulating EPA proportions among participants with the rs174546_CC genotype and an average 7.8% increase among participants with the TT genotype. Conclusions: Carriers of the T allele at FADS1 rs174546 may need higher doses of dietary EPA and DHA to achieve the same circulating proportions of EPA as carriers of the C allele. The implications of these findings on disease risk and dietary guidelines require further study.
Background: Polyunsaturated fatty acids (PUFAs) are associated with a lower risk of multiple diseases. Fatty acid desaturase 1 gene (FADS1) polymorphisms and dietary PUFA intake are both established determinants of circulating PUFA proportions. Objective: We explored the joint effects of FADS1 polymorphisms and dietary PUFA intake on circulating PUFA proportions. Design: We studied 2288 participants from a nested case-control study of coronary artery disease among participants who provided blood samples in the Nurses' Health Study and the Health Professionals Follow-Up Study. Dietary PUFA intake was obtained from semiquantitative food-frequency questionnaires. FADS1rs174546 was genotyped by using the Affymetrix 6.0 platform, and circulating PUFA proportions were measured with gas-liquid chromatography. Linear regression models were used to examine the associations between rs174546 and circulating proportions of each fatty acid. Gene-diet interactions were tested by including a cross-product term of dietary intake of each PUFA by rs174546 genotype in the linear regression models. Results: After adjustment for sex and ancestry, each copy of the C allele of rs174546 was associated with higher circulating proportions of arachidonic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) and lower proportions of linoleic acid and α-linolenic acid. The magnitude of positive association between higher consumption of dietary EPA or DHA and circulating proportions of EPA increased with each copy of the rs174546_T allele (P-interaction = 0.01 and 0.007, respectively). Each 1-SD increment in EPA intake was associated with an average 3.7% increase in circulating EPA proportions among participants with the rs174546_CC genotype and an average 7.8% increase among participants with the TT genotype. Conclusions: Carriers of the T allele at FADS1rs174546 may need higher doses of dietary EPA and DHA to achieve the same circulating proportions of EPA as carriers of the C allele. The implications of these findings on disease risk and dietary guidelines require further study.
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