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Estrogen receptor 1 gene polymorphisms and decreased risk of obesity in women.

ABSTRACT: Estrogen receptor alpha gene (ESR1) polymorphisms have been associated with several diseases, but whether they are associated with obesity is uncertain. To elucidate the role of genetic variation in the ESR1 gene with body mass index (BMI), 543 white women (median age, 63 years) from the Women's Health Study were examined. Most were postmenopausal (99.3%). The relationships between rs2234693 and rs9340799 genotypes and their associated haplotypes with obesity (BMI > or =30 kg/m(2)) and overweight (BMI > or =25 kg/m(2)) were evaluated. Among women with the rs2234693 TT genotype, 18.3% were obese, whereas only 8.2% of those with the CC genotype were obese (P = .04). In a logistic regression model assuming additive inheritance, rs2234693 was associated with decreased odds of obesity (BMI > or =30 kg/m(2)) (crude odds ratio = 0.63, 95% confidence interval = 0.44-0.90, P = .01). For rs9340799, only an inverse trend was observed for BMI (P = .08). Haplotypes that included the variant C allele were associated with a reduced risk of obesity (crude odds ratio = 0.65, 95% confidence interval = 0.44-0.94, P = .02 for C-G). The rs2234693 C allele of ESR1 and its associated genotypes and haplotypes were inversely and consistently associated with obesity. One or more copies of the C allele were associated with decreased risk of obesity in white postmenopausal women.

SUBMITTER: Goulart AC

PROVIDER: S-EPMC2730211 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Estrogen receptor 1 gene polymorphisms and decreased risk of obesity in women.

Goulart Alessandra C AC Zee Robert Y L RY Rexrode Kathryn M KM

Metabolism: clinical and experimental 20090601 6

Estrogen receptor alpha gene (ESR1) polymorphisms have been associated with several diseases, but whether they are associated with obesity is uncertain. To elucidate the role of genetic variation in the ESR1 gene with body mass index (BMI), 543 white women (median age, 63 years) from the Women's Health Study were examined. Most were postmenopausal (99.3%). The relationships between rs2234693 and rs9340799 genotypes and their associated haplotypes with obesity (BMI > or =30 kg/m(2)) and overweigh ...[more]

PMID: 19375130

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Project description:BACKGROUND: The estrogen receptors alpha and beta (ESR1, ESR2) have been implicated in adiposity, lipid metabolism and feeding behaviour. In this report we analyse ESR1 and ESR2 gene single nucleotide polymorphisms (SNPs) for association with obesity. We also relate adipose tissue ESR1 mRNA levels and ESR1 SNPs to adipocyte lipolysis and lipogenesis phenotypes. METHODS: 23 ESR1 and 11 ESR2 tag-SNPs, covering most of the common haplotype variation in each gene according to HAPMAP data, were analysed by Chi2 for association with obesity in a cohort comprising 705 adults with severe obesity and 402 lean individuals. Results were replicated in a cohort comprising 837 obese and 613 lean subjects. About 80% of both cohorts comprised women and 20% men. Adipose tissue ESR1 mRNA was quantified in 122 women and related to lipolysis and lipogenesis by multiple regression. ESR1 SNPs were analysed for association with adipocyte lipolysis and lipogenesis phenotypes in 204 obese women by simple regression. RESULTS: No ESR1 SNP was associated with obesity. Five ESR2 SNPs displayed nominal significant allelic association with obesity in women and one in men. The two ESR2 SNPs associated with obesity with nominal P value < 0.01 were genotyped in a second cohort where no association with obesity was observed. There was an inverse correlation between ESR1 mRNA levels in abdominal subcutaneous (sc) adipose tissue and basal lipolysis, as well as responsiveness to adrenoceptor agonists independent of age and BMI (P value 0.009-0.045). ESR1 rs532010 was associated with lipolytic sensitivity to noradrenaline (nominal P value 0.012), and ESR1 rs1884051 with responsiveness to the non-selective beta-adrenoceptor agonist isoprenaline (nominal P value 0.05). These associations became non-significant after Bonferroni correction. CONCLUSION: ESR1 gene alleles are unlikely to be a major cause of obesity in women. A minor importance of ESR2 on severe obesity cannot be excluded. The inverse correlation between ESR1 mRNA levels and lipolytic responsiveness to adrenoceptor agonists implies that low adipose tissue ESR1 levels attenuate catecholamine resistance in sc fat cells of obese women hereby contributing to loss of sc and gain of visceral fat. There is no evidence for a genetic impact of ESR1 on lipolysis or lipogenesis.

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Estrogen receptor 1 gene polymorphisms and decreased risk of obesity in women.

Publications

Estrogen receptor 1 gene polymorphisms and decreased risk of obesity in women.

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