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Gene expression in subcutaneous adipose tissue differs in women with polycystic ovary syndrome and controls matched pair-wise for age, body weight, and body mass index.

ABSTRACT: Adipose tissue dysfunction may be a central factor in the pathogenesis of insulin resistance in women with polycystic ovary syndrome (PCOS). Gene expression in subcutaneous adipose tissue in PCOS and its relation to metabolic and endocrine features of the syndrome have been fragmentarily investigated. The aim was to assess in subcutaneous adipose tissue the expression of genes potentially associated with adipose tissue dysfunction and to explore their relation to features of the syndrome. Twenty-one women with PCOS (body mass index [BMI] 18.2-33.4 kg/m(2)) and 21 controls (BMI 19.2-31.7 kg/m(2)) were matched pair-wise for age, body weight, and BMI. Tissue biopsies were obtained to measure mRNA expression of 44 genes (TaqMan Low Density Array). Differential expression levels were correlated with BMI, glucose infusion rate (GIR), sex hormone binding globulin (SHBG), and sex steroids. In PCOS, expression of adiponectin receptor 2 (ADIPOR2), LPL, and twist-related protein 1 (TWIST1) was decreased, while expression of chemokine (C-C motif) ligand 2 (CCL2) and heme oxygenase (decycling 1) (HMOX1) was increased. TWIST1 and HMOX1, both novel adipokines, correlated with BMI and GIR. After BMI adjustment, LPL and ADIPOR2 expression correlated with plasma estradiol, and CCL2 expression correlated with GIR, in all women. We conclude that adipose tissue mRNA expression differed in PCOS women and controls and that two novel adipokines, TWIST1 and HMOX1, together with adiponectin, LPL, and CCL2, and their downstream pathways merit further investigation.

SUBMITTER: Manneras-Holm L

PROVIDER: S-EPMC4110095 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Gene expression in subcutaneous adipose tissue differs in women with polycystic ovary syndrome and controls matched pair-wise for age, body weight, and body mass index.

Mannerås-Holm Louise L Benrick Anna A Stener-Victorin Elisabet E

Adipocyte 20140404 3

Adipose tissue dysfunction may be a central factor in the pathogenesis of insulin resistance in women with polycystic ovary syndrome (PCOS). Gene expression in subcutaneous adipose tissue in PCOS and its relation to metabolic and endocrine features of the syndrome have been fragmentarily investigated. The aim was to assess in subcutaneous adipose tissue the expression of genes potentially associated with adipose tissue dysfunction and to explore their relation to features of the syndrome. Twenty ...[more]

PMID: 25068085

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Project description:Study questionWhat are the causal relationships between polycystic ovary syndrome (PCOS) and body mass index (BMI)?Summary answerBidirectional Mendelian randomization analyses suggest that increased BMI is causal for PCOS while the reverse is not the case.What is known alreadyThe contribution of obesity to the pathogenesis of PCOS is controversial. To date, published genetic studies addressing this question have generated conflicting results and have not utilized the full extent of known single nucleotide polymorphisms associated with body mass index (BMI).Study design, size, durationThis cross-sectional Mendelian randomization (MR) and genetic association study was conducted in 750 individuals of European origin and with PCOS and 1567 BMI-matched controls.Participants/materials, setting, methodsCases and controls were matched for BMI as well as for distribution of weight categories (normal weight, overweight, obese). Two-sample MR using inverse variance weighting (IVW) was conducted using a 92-SNP instrument variable for BMI with PCOS as the outcome, followed by two-sample MR with a 16-SNP instrument variable for PCOS with BMI as the outcome. Sensitivity analyses included MR-Egger and maximum likelihood methods. Secondary analyses assessed associations of genetic risk scores and individual SNPs with PCOS, BMI and quantitative androgen-related and glucose homeostasis-related traits.Main results and the role of chanceEach standard deviation genetically higher BMI was associated with a 4.89 (95% CI 1.46-16.32) higher odds of PCOS. Conversely, genetic risk of PCOS did not influence BMI. Sensitivity analyses yielded directionally consistent results. The genetic risk score of 92 BMI SNPs was associated with the diagnosis of PCOS (OR 1.043, 95% CI 1.009-1.078, P = 0.012). Of the 92 BMI risk variants evaluated, none were associated individually with PCOS after considering multiple testing. The association of FTO SNP rs1421085 with BMI was stronger in women with PCOS (β = 0.071, P = 0.0006) than in controls (β = 0.046, P = 0.065).Limitations, reasons for cautionThe current sample size, while providing good power for MR and genetic risk score analyses, had limited power to demonstrate association of individual SNPs with PCOS. Cases and controls were not matched for age; however, this was mitigated by adjusting analyses for age. Dietary and lifestyle data, which could have been used to explore the greater association of the FTO SNP with BMI in women with PCOS, was not available.Wider implications of the findingsIncreasing BMI appears to be causal for PCOS but having PCOS does not appear to affect BMI. This study used the most comprehensive set of SNPs for BMI currently available. Prior studies using fewer SNPs had yielded conflicting results and may have been confounded because cases and controls were not matched for weight categories. The current results highlight the potential utility of weight management in the prevention and treatment of PCOS.Study funding/competing interest(s)National Institutes of Health Grants R01-HD29364 and K24-HD01346 (to R.A.), Grant R01-DK79888 (to M.O.G.), Grant U54-HD034449 (to R.S.L.), Grant U19-HL069757 (to R.M.K.). The funders had no influence on the data collection, analyses or conclusions of the study. No conflict of interests to declare.Trial registration numberN/A.

Dataset Information

Gene expression in subcutaneous adipose tissue differs in women with polycystic ovary syndrome and controls matched pair-wise for age, body weight, and body mass index.

Publications

Gene expression in subcutaneous adipose tissue differs in women with polycystic ovary syndrome and controls matched pair-wise for age, body weight, and body mass index.

Similar Datasets

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