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lüll The molecular-genetic basis of functional hyperandrogenism and the polycystic ovary syndrome Escobar-Morreale HF; Luque-Ramirez M; San Millan JLEndocr Rev 2005[Apr]; 26 (2): 251-82The genetic mechanisms underlying functional hyperandrogenism and the polycystic ovary syndrome (PCOS) remain largely unknown. Given the large number of genetic variants found in association with these disorders, the emerging picture is that of a complex multigenic trait in which environmental influences play an important role in the expression of the hyperandrogenic phenotype. Among others, genomic variants in genes related to the regulation of androgen biosynthesis and function, insulin resistance, and the metabolic syndrome, and proinflammatory genotypes may be involved in the genetic predisposition to functional hyperandrogenism and PCOS. The elucidation of the molecular genetic basis of these disorders has been burdened by the heterogeneity in the diagnostic criteria used to define PCOS, the limited sample size of the studies conducted to date, and the lack of precision in the identification of ethnic and environmental factors that trigger the development of hyperandrogenic disorders. Progress in this area requires adequately sized multicenter collaborative studies after standardization of the diagnostic criteria used to classify hyperandrogenic patients, in whom modifying environmental factors such as ethnicity, diet, and lifestyle are identified with precision. In addition to classic molecular genetic techniques such as linkage analysis in the form of a whole-genome scan and large case-control studies, promising genomic and proteomic approaches will be paramount to our understanding of the pathogenesis of functional hyperandrogenism and PCOS, allowing a more precise prevention, diagnosis, and treatment of these prevalent disorders.|Androgens/genetics[MESH]|Female[MESH]|Genetic Linkage/physiology[MESH]|Humans[MESH]|Hyperandrogenism/*genetics/metabolism[MESH]|Insulin Resistance/genetics/physiology[MESH]|Polycystic Ovary Syndrome/*genetics/metabolism[MESH] |