Genetic variants in peroxisome proliferator-activated receptor gamma influence insulin resistance and testosterone levels in normal women, but not those with polycystic ovary syndrome.
OBJECTIVE
To investigate the relationship of the peroxisome proliferator-activated receptor gamma (PPARG) Pro12Ala and silent exon 6 (His447His) polymorphisms with the clinical features of polycystic ovary syndrome (PCOS).


METHODS
Patients with PCOS and control subjects were genotyped for Pro12Ala and His447His. Associations between genotype, diagnosis, and hormonal/metabolic parameters were assessed.


METHODS
Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham, Birmingham, Alabama. Control subjects were recruited from the surrounding community. Genotyping was performed at the Cedars-Sinai Medical Center in Los Angeles, California.


METHODS
Participants included 285 white women with PCOS and 187 controls.


METHODS
None.


METHODS
The Pro12Ala and His447His genotypes, and hormonal and metabolic phenotypes.


RESULTS
The Pro12Ala and His447His genotypes did not influence risk of PCOS or its component phenotypes in patients with PCOS. In controls, Pro12Ala did not influence measures of insulin resistance or androgen production. However, carriers of the His447His T-allele had significantly decreased free and total T levels, and a significantly decreased homeostasis model assessment index of insulin resistance. Furthermore, haplotypes in controls bearing the His447His T-allele were also associated with decreased T.


CONCLUSIONS
Peroxisome proliferator-activated receptor gamma does not appear to be an important modifier gene in PCOS. In controls, however, the His447His T-allele may be in linkage disequilibrium with a functional variant that influences insulin resistance and T production.
Antoine
Heath J
HJ
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Pall
Marita
M
Trader
Belynda C
BC
Chen
Yii-Der I
YD
Azziz
Ricardo
R
Goodarzi
Mark O
MO
D000293:Adolescent; D000328:Adult; D000483:Alleles; D015992:Body Mass Index; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007333:Insulin Resistance; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics*; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D013739:Testosterone / Q000097:blood*
D047495:PPAR gamma; D013739:Testosterone