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FADS1-FADS2 gene cluster confers risk to polycystic ovary syndrome.

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.

SUBMITTER: Tian Y

PROVIDER: S-EPMC4754766 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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FADS1-FADS2 gene cluster confers risk to polycystic ovary syndrome.

Tian Ye Y Zhang Wei W Zhao Shigang S Sun Yinhua Y Bian Yuehong Y Chen Tailai T Du Yanzhi Y Zhang Jiangtao J Wang Zhao Z Huang Tao T Peng Yingqian Y Yang Ping P Zhao Han H Chen Zi-Jiang ZJ

Scientific reports 20160216

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 ...[more]

PMID: 26879377

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Project description:BACKGROUND: Elevated cholesterol levels in children can be a risk factor for cardiovascular diseases in later life. In adults, it has been shown that blood lipid levels are strongly influenced by polymorphisms in the fatty acid desaturase (FADS) gene cluster in addition to nutritional and other exogenous and endogenous determinants. Our aim was to investigate whether lipid levels are determined by the FADS genotype already in children and whether this association interacts with dietary intake of n-3 fatty acids. METHODS: The analysis was based on data of 2006 children from two German prospective birth cohort studies. Total cholesterol, HDL, LDL and triglycerides were measured at 10 years of age. Six single nucleotide polymorphisms (SNPs) of the FADS gene cluster were genotyped. Dietary n-3 fatty acid intake was assessed by food frequency questionnaire. Linear regression modeling was used to assess the association between lipid levels, n-3 fatty acid intake and FADS genotype. RESULTS: Individuals carrying the homozygous minor allele had lower levels of total cholesterol [means ratio (MR) ranging from 0.96 (p?=?0.0093) to 0.98 (p?=?0.2949), depending on SNPs] and LDL [MR between 0.94 (p?=?0.0179) and 0.97 (p?=?0.2963)] compared to homozygous major allele carriers. Carriers of the heterozygous allele showed lower HDL levels [? between -0.04 (p?=?0.0074) to -0.01 (p?=?0.3318)] and higher triglyceride levels [MR ranging from 1.06 (p?=?0.0065) to 1.07 (p?=?0.0028)] compared to homozygous major allele carriers. A higher n-3 PUFA intake was associated with higher concentrations of total cholesterol, LDL, HDL and lower triglyceride levels, but these associations did not interact with the FADS1 FADS2 genotype. CONCLUSION: Total cholesterol, HDL, LDL and triglyceride concentrations may be influenced by the FADS1 FADS2 genotype already in 10 year old children. Genetically determined blood lipid levels during childhood might differentially predispose individuals to the development of cardiovascular diseases later in life.

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FADS1-FADS2 gene cluster confers risk to polycystic ovary syndrome.

Publications

FADS1-FADS2 gene cluster confers risk to polycystic ovary syndrome.

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