Family-Based Analysis of Candidate Genes for Polycystic Ovary Syndrome
Year: 2010
Type: article
Study design: Observational Study
Abstract: CONTEXT: Polycystic ovary syndrome (PCOS) is a complex disorder having both genetic and environmental components. A number of association studies based on candidate genes have reported significant association, but few have been replicated. D19S884, a polymorphic marker in fibrillin 3 (FBN3), is one of the few association findings that has been replicated in independent sets of families. OBJECTIVE: The aims of the study are: 1) to genotype single nucleotide polymorphisms (SNPs) in the region of D19S884; and 2) to follow up with an independent data set, published results reporting evidence for PCOS candidate gene associations. DESIGN: The transmission disequilibrium test (TDT) was used to analyze linkage and association between PCOS and SNPs in candidate genes previously reported by us and by others as significantly associated with PCOS. SETTING: The study was conducted at academic medical centers. PATIENTS OR OTHER PARTICIPANTS: A total of 453 families having a proband with PCOS participated in the study. Sisters with PCOS were also included. There was a total of 502 probands and sisters with PCOS. INTERVENTION(S): There were no interventions. MAIN OUTCOME MEASURE(S): The outcome measure was transmission frequency of SNP alleles. RESULTS: We identified a six-SNP haplotype block spanning a 6.7-kb region on chromosome 19p13.2 that includes D19S884. SNP haplotype allele-C alone and in combination with D19S884-allele 8 is significantly associated with PCOS: haplotype-C TDT chi(2) = 10.0 (P = 0.0016) and haplotype-C/A8 TDT chi(2) = 7.6 (P = 0.006). SNPs in four of the other 26 putative candidate genes that were tested using the TDT were nominally significant (ACVR2A, POMC, FEM1B, and SGTA). One SNP in POMC (rs12473543, chi(2) = 9.1; P(corrected) = 0.042) is significant after correction for multiple testing. CONCLUSIONS: A polymorphic variant, D19S884, in FBN3 is associated with risk of PCOS. POMC is also a candidate gene of interest.
DOI: 10.1210/jc.2009-2703
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: University of Pennsylvania, Northwestern University, Pennsylvania State University, National Institutes of Health, National Center for Research Resources, NIH Clinical Center, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1026247591, G1370328581, G15008644, Genes, Androgens and Intrauterine Environment in PCOS, G251845744, G281275239, G3088804958, General Clinical Research Center, G3551503464, The Inflammatory Response Pathway in the Etiology of Polycystic Ovary Syndrome, Mechanism of Metformin Action in Normal and PCOS Theca Cells, G424215407, G491532010, G505760010, G5259499678, G5825670501, G6783814425, Translational Research in Polycystic Ovary Syndrome, Multidisciplinary Clinical and Translational Science (MCTS) Program (UL1), GENERAL CLINICAL RESEARCH CENTER, G8867394933
OpenAlex ID: W2021881867