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Association of genetic polymorphisms in CYP19A1 and blood levels of sex hormones among postmenopausal Chinese women.

ABSTRACT: Circulating estrogen levels have been related to the risk of several female cancers. Blood levels of estrogen are controlled by estrogen synthesis enzymes. Genetic variation of estrogen genes thus may influence circulating estrogen levels. We investigated the associations of genetic polymorphisms in CYP19A1, a critical gene involved in estrogen synthesis, with plasma levels of sex hormones among postmenopausal Chinese women.Included in this study were 345 postmenopausal community controls from a population-based case-control study conducted in Shanghai. Fasting blood samples from those women were measured for blood estradiol, estrone, estrone sulfate, and testosterone. A total of 19 genetic polymorphisms in CYP19A1 were genotyped using ABI7900 or PCR-restriction fragment length polymorphism methods. Differences in plasma levels of hormones by genotype were examined using variance analysis.The geometric means of plasma levels of estradiol, estrone, estrone sulfate, and testosterone were 10.1, 16.8, 969.0, and 202.9 pg/ml, respectively, for this study population. We found that plasma levels of estrone were associated with rs28566535 (P=0.0180), rs730154 (P=0.0141), and rs936306 (P=0.0274) in block 2. In the same block, the haplotype CGCTA was related to level of estrone (P=0.0064). Single nucleotide polymorphism rs1902584 in block 1 was associated with estradiol only in overweight postmenopausal women. No clear association with sex hormones was noted for the other genetic polymorphisms evaluated in the study.Single nucleotide polymorphisms in blocks 1 and 2 of the CYP19A1 gene are related to plasma levels of estrogen among postmenopausal Chinese women and may therefore play an important role in the etiology of hormone-related cancers.

SUBMITTER: Cai H

PROVIDER: S-EPMC2613759 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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Association of genetic polymorphisms in CYP19A1 and blood levels of sex hormones among postmenopausal Chinese women.

Cai Hui H Shu Xiao Ou XO Egan Kathleen M KM Cai Qiuyin Q Long Ji-Rong JR Gao Yu-Tang YT Zheng Wei W

Pharmacogenetics and genomics 20080801 8

<h4>Objective</h4>Circulating estrogen levels have been related to the risk of several female cancers. Blood levels of estrogen are controlled by estrogen synthesis enzymes. Genetic variation of estrogen genes thus may influence circulating estrogen levels. We investigated the associations of genetic polymorphisms in CYP19A1, a critical gene involved in estrogen synthesis, with plasma levels of sex hormones among postmenopausal Chinese women.<h4>Methods</h4>Included in this study were 345 postme ...[more]

PMID: 18622258

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Project description:BackgroundThe relationship between CYP19A1 genetic polymorphisms and coronary artery disease (CAD) remains unclear. Thus, the aim of the present study was to investigate the association of CYP19A1 genetic polymorphisms with CAD in Han and Uygur populations and to characterize the association between the levels of sex hormones and aromatase with single-nucleotide polymorphisms (SNPs) in CYP19A1 genes in Chinese women.ResultsThere were significant differences in the genotype distributions of rs2236722 and rs4646 between CAD patients and control subjects in the Uygur population. The rs4646 was found to be associated with CAD in the dominant model (CC vs. CA + AA) and the additive model (CA vs. CC + AA) (both P ≤ 0.001). The difference remained statistically significant after multivariate adjustment (OR = 0.483, 95% CI: 0.338-0.690, P = 0.000; and OR = 1.844, 95% CI: 1.300-2.617, P = 0.001, respectively). In normal Uygur postmenopausal women, there were significant differences in the genotype distributions of rs4646 and the circulating hormone and aromatase levels between CAD patients and control subjects. The differences in estradiol and aromatase levels remained statistically significant after multivariate adjustment (OR = 0.889, 95% CI: 0.817-0.969, P = 0.007; and OR = 0.947, 95% CI: 0.936-0.957, P = 0.000, respectively). Additionally, there were differences in sex hormone levels between the different ethnicities among the Xinjiang Chinese population.Materials and methodsAmong a total of 1,064 Han individuals (614 men and 450 women) and 790 Uygur individuals (484 men and 306 women), 498 postmenopausal women (265 Han and 233 Uygur individuals) were selected. Four SNPs (rs2236722, rs2304463, rs4646, and rs4275794) were genotyped using the improved multiplex ligation detection reaction (iMLDR) technique. The estradiol and testosterone levels were determined using a radioimmunoassay based on GC-2016γ. In addition, an enzyme-linked immunosorbent assay (ELISA) was performed to determine the serum P450 aromatase levels.ConclusionsThe results of this study indicate that the rs2236722 and rs4646 of the CYP19A1 gene are associated with CAD and circulating sex hormone levels in the Xinjiang population of China.

Project description:The aim of the study was to compare the effects of vitamin D3 supplementation versus placebo on serum sex hormones in postmenopausal women completing a 12-month diet + exercise weight loss program.Two hundred eighteen overweight or obese women (50-75 y) with serum 25-hydroxyvitamin D at least 10 to less than 32?ng/mL ("insufficient") were randomized to either weight loss + 2,000?IU/day oral vitamin D3, or to weight loss + daily placebo. Serum sex hormone-binding globulin, estrone, total, free, and bioavailable estradiol, and testosterone were measured by radioimmunoassay before randomization and at 12 months. Mean changes were compared between groups (intent-to-treat) using generalized estimating equations.The 12-month changes in sex hormone-binding globulin, estrone, total, free, and bioavailable estradiol, and testosterone did not differ between groups (all P?>?0.05). However, a greater increase in serum 25-hydroxyvitamin D was associated with a greater increase in sex hormone-binding globulin (Ptrend?=?0.01), and larger decreases in free and bioavailable estradiol (Ptrend?=?0.04, Ptrend?=?0.03, respectively). In post-hoc analyses, we compared women randomized to vitamin D whose serum 25-hydroxyvitamin D remained insufficient (n?=?38), to women who became replete (25-hydroxyvitamin D ?32?ng/mL; n?=?53). Replete women showed greater reductions in bioavailable estradiol (-1.8 vs -0.7?pg/mL), free testosterone (-0.8 vs -0.3?pg/mL), and bioavailable testosterone (-1.8 vs -0.6?ng/dL), and a greater increase in sex hormone-binding globulin (10.6 vs 4.7?nmol/L) (all P?<?0.05), even after adjusting for differences in total 12-month weight loss.Overall, 12-month changes in sex hormone did not differ between groups. However, vitamin D repletion was associated with greater reductions in sex hormones during weight loss, with a possible dose-dependent effect. Future studies should test higher doses and target circulating 25-hydroxyvitamin D levels when measuring such effects.

Dataset Information

Association of genetic polymorphisms in CYP19A1 and blood levels of sex hormones among postmenopausal Chinese women.

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Association of genetic polymorphisms in CYP19A1 and blood levels of sex hormones among postmenopausal Chinese women.

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