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Title: Fatty acid desaturase gene variants, cardiovascular risk factors, and myocardial infarction in the costa rica study

Author
item ASLIBEKYAN, STELLA - Brown University
item JENSEN, MAJKIN - Harvard School Of Public Health
item CAMPOS, HANNIA - Harvard School Of Public Health
item LINKLETTER, CRYSTAL - Brown University
item LOUCKS, ERIC - Brown University
item ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item DEKA, RANJAN - University Of Cincinnati
item RIMM, ERIC - Harvard School Of Public Health
item BAYLIN, ANA - University Of Michigan

Submitted to: Frontiers in Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/3/2011
Publication Date: 5/3/2012
Citation: Aslibekyan, S., Jensen, M.K., Campos, H., Linkletter, C.D., Loucks, E.B., Ordovas, J.M., Deka, R., Rimm, E.B., Baylin, A. 2012. Fatty acid desaturase gene variants, cardiovascular risk factors, and myocardial infarction in the costa rica study. Frontiers in Genetics. 3:72.

Interpretive Summary: Fatty acid desaturases (FADS) are enzymes that regulate unsaturation of fatty acids through the introduction of double bonds between defined carbons of the fatty acyl chain. Genetic variation in FADS has previously been linked to long-chain polyunsaturated fatty acids (PUFAs) in adipose tissue and cardiovascular risk. The objective of our study was to test associations between six common FADS polymorphisms (rs174556, rs3834458, rs174570, rs2524299, rs174589, rs174627), cardiovascular risk factors, and non-fatal heart attack in a case-control study of Costa Rican adults (n'='1756). Moreover, analyses involving cardiovascular risk factors and MI were also conducted in two replication cohorts, The Nurses' Health Study (n'='1200) and The Health Professionals Follow-Up Study (n'='1295). In the Costa Rica Study, genetic variation in the FADS cluster was inversely associated with adipose gamma-linolenic, arachidonic, and eicosapentaenoic fatty acids, and positively associated with eicosadienoic, eicosatrienoic, and dihomo-gamma-linolenic fatty acids. However, these associations did not translate into changes in inflammatory biomarkers, blood lipids, or the risk of heart attack in these cohorts. Therefore, FADS polymorphisms impact long-chain PUFA biosynthesis, but their overall effect on cardiovascular health merits further investigation.

Technical Abstract: Genetic variation in fatty acid desaturases (FADS) has previously been linked to long-chain polyunsaturated fatty acids (PUFAs) in adipose tissue and cardiovascular risk. The goal of our study was to test associations between six common FADS polymorphisms (rs174556, rs3834458, rs174570, rs2524299, rs174589, rs174627), intermediate cardiovascular risk factors, and non-fatal myocardial infarction (MI) in a matched population based case-control study of Costa Rican adults (n'='1756). Generalized linear models and multiple conditional logistic regression models were used to assess the associations of interest. Analyses involving intermediate cardiovascular risk factors and MI were also conducted in two replication cohorts, The Nurses' Health Study (n'='1200) and The Health Professionals Follow-Up Study (n'='1295). In the Costa Rica Study, genetic variation in the FADS cluster was associated with a robust linear decrease in adipose gamma-linolenic, arachidonic, and eicosapentaenoic fatty acids, and significant or borderline significant increases in the eicosadienoic, eicosatrienoic, and dihomo-gamma-linolenic fatty acids. However, the associations with adipose tissue fatty acids did not translate into changes in inflammatory biomarkers, blood lipids, or the risk of MI in the discovery or the replication cohorts. In conclusion, fatty acid desaturase polymorphisms impact long-chain PUFA biosynthesis, but their overall effect on cardiovascular health likely involves multiple pathways and merits further investigation.