Identification of Genetic Risk Factors for BPH.

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Despite years of intensive investigations, the etiology of benign prostatic hyperplasia (BPH) is still uncertain. To date, however, the powerful tools of molecular genetics have not been extensively used to investigate these mechanisms. In particular, genetic association is a powerful approach to identify genes and/or genetic loci that confer disease susceptibility. Family and twin studies by our group and others have provided strong evidence for genetics as an important factor in the development of BPH. These intriguing findings of a genetic susceptibility to BPH suggests that there are germline sequence variants in the genome predisposing to the disease. We feel that there is enough evidence for an important genetic component of BPH to justify a systematic search to identify BPH susceptibility alleles, and that progress in genome wide association technology makes such a search highly lil<ely to yield valuable results. Single nucleotide polymorphisms (SNPs) may be directly associated with BPH risk or indirectly associated with BPH risk through linkage disequilibrium (LD) with a causal sequence variant. These risk-associated SNPs will have different genotype frequencies among men with or without BPH and can be detected using genetic association studies. We propose to test the hypothesis that commonly occurring genetic variants exist in the population which are associated with increases in risk for BPH. The goal ofthis study is to identify and characterize these BPH susceptibility loci. To accomplish this goal, we propose to carry out a genome wide association study and confirming follow up analyses in men with and without BPH. Once identified, these loci will provide the basis for functional studies to characterize the role of these loci in the development of BPH. Understanding the molecular etiology ofthis disease will have important clinical consequences in terms of developing novel preventive and therapeutic approaches for this common disease.