Genetic Variants of the Fatty Acid Desaturase Gene Cluster Are Associated with Plasma LDL Cholesterol Levels in Japanese Males

Abstract

Fatty acid (FA) compositions in tissues are related to metabolic disorders, and consequently the appropriate management of underlying FA compositions in tissues is considered to be important. However, the relationship among the serum lipid profiles, the FA composition of the red blood cell (RBC) membranes and genetic variations in the fatty acid desaturase (FADS) genes in Japanese men is unclear. In this study, the subjects recruited were 137 Japanese men, 40 to 60 y old, who had a regular health checkup. Their serum lipid profile and the relative FA composition of the RBC membranes were measured. They were genotyped for the single nucleotide polymorphisms (SNPs) rs174553, rs174546, rs99780 and rs174583 in FADS gene. Multiple regression analysis was conducted to detect the relationship among hyperlipidemia, the FA composition of the RBC and the FADS genotypes. As a result, the homozygous genotype for the minor alleles in rs174553, rs174546, rs99780 were found to be associated with lower low-density lipoprotein cholesterol (LDL-C) levels and a lower LDL-C/total-cholesterol ratio. The homozygous genotype for the minor alleles reduced the risk of high LDL-C level (R2=0.50, β=-0.20, p=0.009), whereas, the arachidonic acid (AA) levels in the carriers of the homozygous genotype for the minor alleles tended to be lower compared with the carriers of the major alleles. However, no significant differences were observed in any FA level among the three genotypes for four SNPs. These results indicate that the appropriate management of serum LDL-C levels depending on genetic predisposition in FADS genotypes should be encouraged.

Effects of Metformin on Metabolite Profiles and LDL Cholesterol in Patients With Type 2 Diabetes

“…It has been suggested that lower levels of arachidonic acid leads to an increased membrane fluidity, thus increasing LDL-C receptor recycling (35). This hypothesis is especially strong, given that genetic variants assigned to lower activity of FADS1 and -2 were significantly associated with lower LDL-C levels (36).…”

“…activity and consequently reduction of the levels of PUFA, namely, arachidonic acid (35). It has been suggested that lower levels of arachidonic acid leads to an increased membrane fluidity, thus increasing LDL-C receptor recycling (35).…”

Efficacy of Habitual Exercise for Improving Lipid Profiles Depends on the PPRA^|^gamma; Genotype in Japanese Males

“…Consequently, 138 participants (74 with waist circumferences ,85 cm and 64 with waist circumferences 85 cm) were included in this study. Details regarding the characteristics of the participants were as previously described (5). The study protocol adhered to the Japanese Government's Ethical Guidelines Regarding Epidemiological Studies, in accordance with the Declaration of Helsinki, and the study was approved by the Institutional Review Board of Human Genome Research Ethics at the Institute of Life and Environmental Science for Human Life, Ochanomizu University, Japan.…”

“…acid (FA) desaturase, perilipin, and hormone-sensitive lipase genes alter obesity-inducible lipid profiles in Japanese males (5,6). However, the association of obesity with PPARg variants has not been clarified in Japanese males.…”

Statins Plus Metformin: a Promising Combination for Prevention and Treatment of Atherosclerosis

“…It was believed that the effect of metformin was associated with adenosine 5-monophosphateactivated protein kinase (AMPK), AMPK activated by metformin can suppress fatty acid desaturases (FADS) synthesis in liver 6. It has been suggested that down-regulation of FADS could lower levels of arachidonic acid, leading to an increased membrane fluidity, and subsequently increases LDL receptor recycling, which accelerated the clearance of serum LDL-C. 8 Thus, AMPK pathway may be the mechanism to clarify the benefits of additional lipid lowering effect of statins plus metformin strategy.…”