Lipoprotein profiles in Mexican American and non-Hispanic white women with polycystic ovary syndrome

Abstract Context: Adrenal androgen excess is common in polycystic ovary syndrome (PCOS) and appears to be heritable. CYP3A7 metabolizes dehydroepiandrosterone and its sulfate (DHEAS). A promoter variant, CYP3A7*1C, which results in persistent expression in adults, was associated with reduced DHEAS levels in a previous study, which led us to consider CYP3A7*1C as a modulator of adrenal androgen excess in patients with PCOS. Objective: The objective was to replicate the association between CYP3A7*1C and reduced DHEAS levels in PCOS patients and assess its possible role in modulating testosterone levels. Design: Women with and without PCOS were genotyped for CYP3A7*1C, and this variant was tested for association with DHEAS and total and free testosterone. Setting: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; controls were recruited from the surrounding community. Genotyping took place at Cedars-Sinai Medical Center (Los Angeles, CA). Participants: A total of 287 white women with PCOS and 187 controls were studied. Main Measurements: CYP3A7*1C genotype, PCOS risk, and androgen levels were measured. Results: PCOS subjects who carried the CYP3A7*1C variant had lower levels of serum DHEAS and total testosterone (P = 0.0006 and 0.046, respectively). The variant was not associated with PCOS risk. Conclusion: This study replicated prior work of the association of CYP3A7*1C and decreased DHEAS in a different population of young PCOS women, providing further genetic evidence that CYP3A7 plays a potential role in modulation of DHEAS levels. Adult expression of CYP3A7 may modify the PCOS phenotype by ameliorating adrenal androgen excess.

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Black women with polycystic ovary syndrome (PCOS) have increased risk for metabolic syndrome (MET SYN) and cardiovascular disease (CVD) compared to white women with PCOS

Fertility and Sterility ◽

10.1016/j.fertnstert.2013.07.1707 ◽

2013 ◽

Vol 100 (3) ◽

pp. S100-S101

Author(s):

J.K. Hillman ◽

L.N.C. Johnson ◽

M. Limaye ◽

R.A. Feldman ◽

M. Sammel ◽

...

Keyword(s):

Cardiovascular Disease ◽

Metabolic Syndrome ◽

Black Women ◽

Polycystic Ovary Syndrome ◽

White Women ◽

Polycystic Ovary ◽

Ovary Syndrome ◽

Increased Risk

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Variants in the 5α-Reductase Type 1 and Type 2 Genes Are Associated with Polycystic Ovary Syndrome and the Severity of Hirsutism in Affected Women

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2006-0227 ◽

2006 ◽

Vol 91 (10) ◽

pp. 4085-4091 ◽

Cited By ~ 52

Author(s):

Mark O. Goodarzi ◽

Nissar A. Shah ◽

Heath J. Antoine ◽

Marita Pall ◽

Xiuqing Guo ◽

...

Keyword(s):

Risk Factors ◽

Los Angeles ◽

Single Nucleotide Polymorphisms ◽

Polycystic Ovary Syndrome ◽

White Women ◽

Polycystic Ovary ◽

Nucleotide Polymorphisms ◽

Ovary Syndrome ◽

Single Nucleotide ◽

Control Subjects

Abstract Context: Despite the importance of dihydrotestosterone in androgen action, polymorphisms in the genes for the two isoforms of 5α-reductase (SRD5A1 and SRD5A2) have not been evaluated as risk factors for polycystic ovary syndrome (PCOS). Objective: The objective of the study was to test the hypothesis that haplotypes in the SRD5A1 and SRD5A2 genes are risk factors for PCOS and the severity of hirsutism in affected women. Design: PCOS and control subjects were genotyped for seven single-nucleotide polymorphisms in SRD5A1 and eight single-nucleotide polymorphisms in SRD5A2. Haplotypes were determined and tested for association with PCOS diagnosis and component phenotypes. Setting: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; control subjects were recruited from the general surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles. Participants: A total of 287 White women with PCOS and 187 controls participated. Main Measurements: SRD5A1 and SRD5A2 genotype, quantitative hirsutism score, and hormonal and metabolic phenotypes were assessed. Results: Haplotypes within both genes were associated with PCOS risk. The Leu allele of the Val89Leu variant in SRD5A2 was associated with protection against PCOS; this allele is known to modestly reduce 5α-reductase activity. Haplotypes in SRD5A1 but not SRD5A2 were also associated with the degree of hirsutism in affected women. Conclusions: This study presents genetic evidence suggesting an important role of both isoforms of 5α-reductase in the pathogenesis of PCOS. That only SRD5A1 haplotypes were associated with hirsutism suggests that only this isoform is important in the hair follicle.

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