Polycystic Ovary Syndrome (PCOS) is a common condition of reproductive age women associated with significant morbidity related to menstrual dysfunction, infertility, obesity, hirsutism, and insulin resistance. There is convincing evidence that the condition has a genetic basis. However, previous studies of women with PCOS demonstrates considerable variability in these complex phenotypic traits between affected individuals, with no clear pathophysiologic subsets. In our studies of a large number of patients and controls, each measured trait is distributed broadly in the PCOS population and varies with obesity, suggesting that PCOS is a polygenic and environmentally influenced inherited disease. Thus, defining a family member as simply """"""""affected"""""""" or """"""""unaffected"""""""", as has been done in genetic studies to date, significantly over-simplifies the genetics of the syndrome. A large number of families or affected relative paris will need to be investigated before genetic linkage studies are feasible. The current proposal seeks to quantify the variability of each trait within families in order to accurately plan the appropriate phenotypic characterization and sample size for a definitive affected family member linkage study in the future. Therefore, affected sisters with PCOS will be extensively evaluated to determine the variability of traits within and between families and to determine the most discriminating test for a larger study. In addition, post-menopausal women with a history of pre-menopausal oligomenorrhea and hirsutism will be compared to post-menopausal women with a history of normal cycles to determine the phenotype of affected post-menopausal women and expand the number of family members who can be evaluated. These results will then be used to plan a multi-center affected family member quantitative trait linkage study of PCOS.
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