Two exonic single nucleotide polymorphisms in the microsomal epoxide hydrolase gene are associated with polycystic ovary syndrome.
OBJECTIVE
To determine whether genetic variability in the gene encoding microsomal epoxide hydrolase (EPHX) contributes to individual differences in susceptibility to the development of polycystic ovary syndrome (PCOS).


METHODS
Retrospective case-control study.


METHODS
University-based clinic.


METHODS
One hundred twelve white women with PCOS and 115 healthy controls.


METHODS
None.


METHODS
The presence of two single nucleotide polymorphisms (SNPs), T-->C (Tyr113His) in exon 3 and A-->G (His139Arg) in exon 4, in the EPHX gene. Single point analysis was expanded to pair of loci haplotype analysis to examine the estimated haplotype frequencies of the two SNPs, of unknown phase, in the PCOS and control groups. Estimated haplotype frequencies were assessed using the maximum-likelihood method, using an expectation-maximization algorithm.


RESULTS
Single point allele and genotype distributions in exon 3 and exon 4 of the EPHX gene were not statistically different between the groups. However, according to the haplotype estimation analysis, we observed a significantly elevated frequency of haplotype C-G (His113-Arg139) in the PCOS group versus the control group. The odds ratio for PCOS associated with the low activity haplotype C-G (His113-Arg139) was 2.28 (95% confidence interval 1.1-4.8).


CONCLUSIONS
The use of two intragenic single nucleotide polymorphisms jointly in haplotype analysis of association demonstrated that the genetically determined low activity haplotype C-G (His113-Arg139) was significantly associated with PCOS.
Korhonen
Seija
S
Department of Obstetrics and Gynecology, Kuopio University Hospital, Kuopio, Finland.
Romppanen
Eeva Liisa
EL
Hiltunen
Mikko
M
Helisalmi
Seppo
S
Punnonen
Kari
K
Hippeläinen
Maritta
M
Heinonen
Seppo
S
D016022:Case-Control Studies; D004851:Epoxide Hydrolases / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D015810:Linkage Disequilibrium; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies
D004851:Epoxide Hydrolases