Polycystic ovary syndrome (PCOS) is a common endocrine disorder of women, characterized by excessiveovarian androgen production, amenorrhea, oligomenorrhea, and subfecundity. Genetic variation insusceptibility probably contributes to the risk of PCOS, but no genes have been identified with certainty. Wehave generated strong evidence for the presence of a genetic determinant influencing PCOS susceptibility,located near the marker D19S884, on chromosome 19p13.2. The evidence comes from consistent findingsin our 3 independent studies of a total of 465 families. D19S884 is located in an intron of the fibrillin 3 gene(FBN3). Fibrillin 3-containing microfibrils are present in the ovary in a geographical location to influencefollicular function.It is likely that there are other susceptibility genes, unlinked to FBN3/D19S884. Our long-term goals areto find all the relevant genes, determine how they contribute to susceptibility individually and jointly, andsequence and characterize the susceptibility alleles themselves.
The aims of this project are: 1. Find thedeterminants and identify effects associated with D19S884, the genetic marker we have already identified:what are the 'downstream' effects of variation at D19S884 and neighboring sequences? 2. Investigate othercandidate genes (unlinked to D19S884/FBN3) including PDE8A, by genetic and molecular methods. 3.Extend the genetic analysis from PCOS (a qualitative trait) to PCOS-associated quantitative traits. Toaccomplish these aims, we will use family-based genetic approaches, association studies, and in vitrostudies to probe gene function and identify new candidate genes. We will continue to evaluate geneticvariation in the D19S884 region of FBN3, as well as additional candidate genes, in an independent collectionof PCOS families recruited as part of this project. The findings from these studies will enhance ourunderstanding of the genetics of PCOS, a major contributor to female infertility. Better knowledge of 'PCOSgenes' will also help in predicting responses to treatments for infertility, insulin resistance, and other aspectsof the disease.
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| Du, Ping; Camacho, Fabian; McCall-Hosenfeld, Jennifer et al. (2015) Human Papillomavirus Vaccination Among Adults and Children in 5 US States. J Public Health Manag Pract 21:573-83 |
| Feiner, John R; Gropper, Michael A; Toy, Pearl et al. (2015) A Clinical Trial to Detect Subclinical Transfusion-induced Lung Injury during Surgery. Anesthesiology 123:126-35 |
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