Association study of androgen signaling pathway genes in polycystic ovary syndrome.
OBJECTIVE
To evaluate genes involved in androgen receptor (AR) signaling as candidate genes for polycystic ovary syndrome (PCOS).


METHODS
Two groups of women with PCOS and control women (discovery and replication cohorts), were genotyped for single-nucleotide polymorphisms (SNPs) in eight genes for AR chaperones and co-chaperones: HSPA1A, HSPA8, ST13, STIP1, PTGES3, FKBP4, BAG1, and STUB1. Single-nucleotide polymorphisms were tested for association with PCOS status and with androgenic and metabolic parameters.


METHODS
Tertiary referral center.


METHODS
Discovery cohort: 354 women with PCOS and 161 control women. Replication cohort: 397 women with PCOS and 306 control women.


METHODS
Phenotypic and genotypic assessment.


METHODS
Single-nucleotide polymorphism genotypes, association with PCOS status, and androgenic and metabolic parameters.


RESULTS
In the discovery cohort, FKBP4 SNPs rs2968909 and rs4409904 were associated with lower odds of PCOS. This finding was not confirmed in the replication cohort analysis; however, when combining the two cohorts, rs4409904 was associated with lower odds of PCOS. In subjects with PCOS in the replication cohort as well as in the combined cohort, rs2968909 was associated with lower body mass index.


CONCLUSIONS
Single-nucleotide polymorphisms in FKBP4, which codes for the AR co-chaperone FKBP52, may be associated with PCOS and body mass index in patients with PCOS. The remaining genes studied do not seem to be major contributors to the development of PCOS. These findings warrant confirmation in future studies, and genes encoding other androgen pathway components remain to be studied.
Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California; Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California.
Aline
A
Ketefian
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
Michelle R
MR
Jones
Children's Hospital Oakland Research Institute, Oakland, California.
Ronald M
RM
Krauss
Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, California.
Yii-Der I
YD
Chen
Department of Obstetrics and Gynecology, Pennsylvania State College of Medicine, Hershey, Pennsylvania.
Richard S
RS
Legro
Departments of Obstetrics and Gynecology and Medicine, Georgia Regents University, Augusta, Georgia.
Ricardo
R
Azziz
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address: mark.goodarzi@cshs.org.
Mark O
MO
Goodarzi
D000293:Adolescent; D000328:Adult; D000728:Androgens / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D011085:Polycystic Ovary Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D065840:Protective Factors; D012307:Risk Factors; D015398:Signal Transduction / Q000235:genetics*; D022021:Tacrolimus Binding Proteins / Q000235:genetics*; D062606:Tertiary Care Centers; D055815:Young Adult
D000728:Androgens; D022021:Tacrolimus Binding Proteins; C403485:tacrolimus binding protein 4
PCOS; androgen receptor; chaperones; co-chaperones