Steroidogenic regulatory factor FOS is underexpressed in polycystic ovary syndrome (PCOS) adipose tissue and genetically associated with PCOS susceptibility.
BACKGROUND
Polycystic ovary syndrome (PCOS) is a heterogeneous common genetic disorder characterized by hyperandrogenemia and insulin resistance. Alterations in gene expression profiles of the ovary and adipose tissue identified the candidate gene FBJ murine osteosarcoma viral oncogene homolog (FOS) for further investigation of expression changes in metabolic tissues and genetic studies.


OBJECTIVE
The objective of the study was to confirm the underexpression of the FOS gene in sc adipose and determine whether variants in this gene are risk factors for PCOS.


METHODS
RT-PCR was performed in sc fat from women with and without PCOS. Genotyping of single-nucleotide polymorphisms in the FOS locus was performed to test for association with PCOS.


METHODS
The study was conducted at a tertiary care academic institution.


METHODS
Twenty-two PCOS and 13 control subjects were recruited for gene expression studies. We assembled a discovery genotyping cohort of 354 cases and 161 controls and a replication cohort of 476 cases and 315 controls, all of whom were Caucasian.


METHODS
Gene expression by quantitative real-time RT-PCR, FOS genotype, and PCOS status were measured.


RESULTS
FOS expression was confirmed to be reduced in PCOS adipose tissue. Three single-nucleotide polymorphisms were significantly associated with PCOS in the discovery cohort (rs8006998, P = 0.0031; rs8013918, P = 0.0006; rs8013942, P = 0.0087). rs8006998 was also associated with PCOS in the replication cohort (P = 0.013).


CONCLUSIONS
Differential gene expression in sc fat and genetic association at the FOS locus in PCOS subjects implicates a role for this transcription factor in PCOS. FOS dysfunction may be a common factor between hyperandrogenism and insulin resistance.
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California 90048, USA.
Michelle R
MR
Jones
Gregorio
G
Chazenbalk
Ning
N
Xu
Angela K
AK
Chua
Tamar
T
Eigler
Emebet
E
Mengesha
Yen-Hao
YH
Chen
Jung-Min
JM
Lee
Marita
M
Pall
Xiaohui
X
Li
Yii-Der I
YD
Chen
Kent D
KD
Taylor
Ruchi
R
Mathur
Ronald M
RM
Krauss
Jerome I
JI
Rotter
Richard S
RS
Legro
Ricardo
R
Azziz
Mark O
MO
Goodarzi
D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D015153:Blotting, Western; D015992:Body Mass Index; D015331:Cohort Studies; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004261:DNA Replication; D005260:Female; D015870:Gene Expression / Q000235:genetics / Q000502:physiology; D016762:Genes, fos / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D015810:Linkage Disequilibrium; D011085:Polycystic Ovary Syndrome / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D050151:Subcutaneous Fat / Q000378:metabolism
D012333:RNA, Messenger; D004247:DNA