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.
Highlights
Long-chain omega-3 polyunsaturated fatty acids (PUFAs), obtained either through dietary intake or synthesized endogenously from alpha-linolenic acid (ALA), have long been known to be protective against heart disease, diabetes, and other chronic outcomes (Harris, 2010)
A previous analysis of our data from the Costa Rican population examined the effect of a common single nucleotide polymorphism (SNP) in the FADS2 promoter region on the risk of non-fatal myocardial infarction (MI; Baylin et al, 2007)
The objective of this study is to evaluate the association between genetic variation in the fatty acid desaturases (FADS) cluster, adipose tissue fatty acids, serum lipids, and inflammatory biomarkers, and the risk of MI in a Costa Rican population
Summary
Long-chain omega-3 polyunsaturated fatty acids (PUFAs), obtained either through dietary intake or synthesized endogenously from alpha-linolenic acid (ALA), have long been known to be protective against heart disease, diabetes, and other chronic outcomes (Harris, 2010). Previous studies showed that in populations with low intake of marine fatty acids, dietary intake of ALA confers cardioprotective benefits, either by itself or through conversion to long-chain PUFAs (Baylin et al, 2003). Several studies, including a recent meta-analysis of genome-wide association (GWA) scans, linked polymorphisms in the FADS gene cluster to PUFA concentrations in serum phospholipids and erythrocyte cell membranes in several populations, including Caucasians, East Asians, and African Americans (Malerba et al, 2008; Martinelli et al, 2008; Rzehak et al, 2009; Tanaka et al, 2009; Kwak et al, 2011; Lemaitre et al, 2011; Mathias et al, 2011). A consistent decrease in adipose and plasma PUFA concentrations was observed with an increase in number of copies of the minor allele, the association with MI was not significant (Baylin et al, 2007)
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