Abstract
BackgroundOdd-numbered chain saturated fatty acids (OCSFA) have been associated with potential health benefits. Although some OCSFA (e.g., C15:0 and C17:0) are found in meats and dairy products, sources and metabolism of C19:0 and C23:0 are relatively unknown, and the influence of non-dietary determinants, including genetic factors, on circulating levels of OCSFA is not established.ObjectiveTo elucidate the biological processes that influence circulating levels of OCSFA by investigating associations between genetic variation and OCSFA.DesignWe performed a meta-analysis of genome-wide association studies (GWAS) of plasma phospholipid/erythrocyte levels of C15:0, C17:0, C19:0, and C23:0 among 11,494 individuals of European descent. We also investigated relationships between specific single nucleotide polymorphisms (SNPs) in the lactase (LCT) gene, associated with adult-onset lactase intolerance, with circulating levels of dairy-derived OCSFA, and evaluated associations of candidate sphingolipid genes with C23:0 levels.ResultsWe found no genome-wide significant evidence that common genetic variation is associated with circulating levels of C15:0 or C23:0. In two cohorts with available data, we identified one intronic SNP (rs13361131) in myosin X gene (MYO10) associated with C17:0 level (P = 1.37×10−8), and two intronic SNP (rs12874278 and rs17363566) in deleted in lymphocytic leukemia 1 (DLEU1) region associated with C19:0 level (P = 7.07×10−9). In contrast, when using a candidate-gene approach, we found evidence that three SNPs in LCT (rs11884924, rs16832067, and rs3816088) are associated with circulating C17:0 level (adjusted P = 4×10−2). In addition, nine SNPs in the ceramide synthase 4 (CERS4) region were associated with circulating C23:0 levels (adjusted P<5×10−2).ConclusionsOur findings suggest that circulating levels of OCSFA may be predominantly influenced by non-genetic factors. SNPs associated with C17:0 level in the LCT gene may reflect genetic influence in dairy consumption or in metabolism of dairy foods. SNPs associated with C23:0 may reflect a role of genetic factors in the synthesis of sphingomyelin.
Highlights
The odd-numbered chain saturated fatty acids (OCSFA), i.e., pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0), are found in ruminant foods such as meats or dairy products synthesized by the bacterial flora in the rumen [1] and seafood [2]
We found no genome-wide significant evidence that common genetic variation is associated with circulating levels of C15:0 or C23:0
In two cohorts with available data, we identified one intronic single nucleotide polymorphisms (SNPs) in myosin X gene (MYO10) associated with C17:0 level (P = 1.37×10−8), and two intronic SNP in deleted in lymphocytic leukemia 1 (DLEU1) region associated with C19:0 level (P = 7.07×10−9)
Summary
The odd-numbered chain saturated fatty acids (OCSFA), i.e., pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0), are found in ruminant foods such as meats or dairy products synthesized by the bacterial flora in the rumen [1] and seafood [2]. Genetic factors could influence dietary consumption; for example, single nucleotide polymorphisms (SNPs) associated with reduced lactose tolerance could influence dairy intake and thereby circulating levels of OCSFA. Odd-numbered chain saturated fatty acids (OCSFA) have been associated with potential health benefits. Some OCSFA (e.g., C15:0 and C17:0) are found in meats and dairy products, sources and metabolism of C19:0 and C23:0 are relatively unknown, and the influence of non-dietary determinants, including genetic factors, on circulating levels of OCSFA is not established. Complete funding information for all including studies are provided as supplemental material
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