Identification of Genetic Risk Factors for BPH.

尽管经过多年的深入研究，良性前列腺增生症(BPH)的病因仍不明确。 然而，到目前为止，分子遗传学的强大工具还没有被广泛用于研究 这些机制。特别是，遗传关联是识别基因和/或基因的有效方法 赋予疾病易感性的基因座。我们团队和其他人对家庭和双胞胎的研究提供了强有力的支持 遗传学是BPH发生发展的重要因素的证据。这些耐人寻味的发现 对褐飞虱的遗传易感性表明基因组中存在种系序列变异。 易患这种疾病的。我们认为有足够的证据证明有一个重要的遗传成分 为了证明系统搜索以确定良性前列腺增生症易感等位基因以及全基因组研究进展的合理性 关联技术使这样的搜索变得非常容易，从而产生有价值的结果。单核苷酸 基因多态性(SNPs)可能与BPH风险直接相关，也可能与BPH风险间接相关 通过带有因果序列变体的连锁不平衡(LD)。这些与风险相关的SNPs将具有 患有和不患有BPH的男性之间不同的基因频率，可以用基因检测 协会研究。 我们建议检验这样一种假设，即常见的遗传变异存在于 与良性前列腺增生症风险增加有关。这项研究目的是识别和描述这些良性前列腺增生症 易感基因座。为了实现这一目标，我们建议进行全基因组关联研究，并 确认对患有和不患有前列腺增生症的男性的随访分析。一旦确定，这些基因座将提供基础 用于功能研究，以确定这些基因座在BPH发生发展中的作用。了解 这种疾病的分子病因学将在发展新的方面具有重要的临床后果 预防和治疗这种常见疾病的方法。

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.