A single nucleotide polymorphism in the FADS1/FADS2 gene is associated with plasma lipid profiles in two genetically similar Asian ethnic groups with distinctive differences in lifestyle

Abstract

Recent genome-wide association studies (GWASs) showed that single nucleotide polymorphisms (SNPs) in FADS1/FADS2 were associated with plasma lipid concentrations in populations with European ancestry. We investigated the associations between the SNPs in FADS1/FADS2 and plasma concentrations of triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in two Asian groups, i.e., Japanese and Mongolians. The genotype of rs174547 (T/C), found to be associated with triglyceride and HDL-C concentrations in the GWAS, was determined in 21,004 Japanese and 1,203 Mongolian individuals. Genotype-phenotype association was assessed by using multiple linear regression models, assuming an additive model of inheritance. The copy number of the rs174547 C allele was significantly associated with increased triglyceride levels (P = 1.5 x 10(-6)) and decreased HDL-C levels (P = 0.03) in the Japanese population. On the other hand, in the Mongolian population, the rs174547 C allele copy number was strongly associated with decreased LDL-C levels (P = 2.6 x 10(-6)), but was not associated with triglyceride and HDL-C levels. The linkage disequilibrium pattern and haplotype structures of SNPs around the FADS1/FADS2 locus showed no marked dissimilarity between Japanese and Mongolian individuals. The present data indicate that the FADS1/FADS2 locus can be added to the growing list of loci involved in polygenic dyslipidemia in Asians. Furthermore, the variable effects of FADS1/FADS2 on plasma lipid profiles in Asians may result from differences in the dietary intake of polyunsaturated fatty acids, which serve as substrates for enzymes encoded by FADS1/FADS2.

Genetic variation at the FADS1-FADS2 gene locus influences delta-5 desaturase activity and LC-PUFA proportions after fish oil supplement

“…Recent GWA studies have also identifi ed several genetic loci in the FADS gene cluster that are associated with blood lipid levels (18)(19)(20)(21). However, we were unable to replicate previously reported associations with plasma lipids, particularly LDL-cholesterol ( 13,22,30 ). This most likely relates to the fact that lipids are distal phenotypes that are infl uenced by many genes and environmental factors in addition to desaturase activity, and our study sample lacked the power to detect signifi cant FADS genotype associations at baseline.…”

“…Blood samples for analysis were drawn after a minimum 8 h overnight fast cholesterol (HDL-C) ( 20,21 ), and higher triglyceride concentrations ( 21 ), suggesting that altered desaturase activities may impact plasma lipoprotein levels. Previous studies have suggested that dietary intake of different PUFAs interact with FADS1 variation to affect blood lipids ( 13,22 ).…”

Interaction between a common variant in FADS1 and erythrocyte polyunsaturated fatty acids on lipid profile in Chinese Hans

“…It is possible that the limited sample size and different dyslipidemia pattern may explain the null fi ndings for total and LDL cholesterol in the current study. Furthermore, distinctive diet and lifestyle may also modify the effects of FADS1 on lipid metabolism, even in genetically similar populations ( 12 ), which might serve as another plausible explanation for these studies might be explained by higher conversion rate of 22:5n-3 to DHA in pregnant women but not in general populations ( 10 ). The associations between FADS1 rs174550 and lipids in the current study were in line with results from a meta-analysis of 122,743 nondiabetic participants ( 15 ), although signifi cant associations were also detected between the genetic variant Data are means ± SE or n. P values were adjusted for age, sex, BMI, residence (urban/rural), and region (Beijing/Shanghai) using an additive model.…”

Relationship of lipid regulatory gene polymorphisms and dyslipidemia in a pediatric population: the CASPIAN III study

“…The association of the FADS1 gene variants with serum lipid compositions has been reported by a number of GWAS [14,39,40]. We studied the FADS (rs174547) polymorphism because it was investigated in pediatric populations.…”

“…The fatty acid desaturase 1 (FADS1) gene encodes fatty acid desaturase enzymes which regulates the desaturation of fatty acids [14].…”