FADS1-FADS2 gene cluster confers risk to polycystic ovary syndrome

Sci Rep. 2016 Feb 16:6:21195. doi: 10.1038/srep21195.

Abstract

Dyslipidemia is common in polycystic ovary syndrome (PCOS). This study was aimed to investigate whether fatty acid desaturase genes (FADS), a dyslipidemia-related gene cluster, are associated with PCOS. We scanned variations of FADS genes using our previous data of genome-wide association study (GWAS) for PCOS and selected rs174570 for further study. The case-control study was conducted in an independent cohort of 1918 PCOS cases and 1889 age-matched controls and family-based study was conducted in a set of 243 core family trios with PCOS probands. Minor allele frequency (allele T) of rs174570 was significantly lower in PCOS cases than that in age-matched controls (P = 2.17E-03, OR = 0.85), even after adjustment of BMI and age. PCOS subjects carrying CC genotype had higher testosterone level and similar lipid/glucose level compared with those carrying TT or TC genotype. In trios, transmission disequilibrium test (TDT) analysis revealed risk allele C of rs174570 was significantly over-transmitted (P = 2.00E-04). Decreased expression of FADS2 was detected in PCOS cases and expression quantitative trait loci (eQTL) analysis revealed the risk allele C dosage was correlated with the decline of FADS2 expression (P = 0.002). Our results demonstrate that FADS1-FADS2 are susceptibility genes for PCOS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Case-Control Studies
  • Delta-5 Fatty Acid Desaturase
  • Fatty Acid Desaturases / genetics*
  • Female
  • Gene Expression
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Linkage Disequilibrium
  • Multigene Family*
  • Polycystic Ovary Syndrome / genetics*
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci
  • RNA, Messenger / genetics
  • Risk
  • Young Adult

Substances

  • Delta-5 Fatty Acid Desaturase
  • RNA, Messenger
  • Fatty Acid Desaturases
  • FADS1 protein, human
  • FADS2 protein, human