Identification of Genetic Risk Factors for BPH.

尽管多年来的深入研究，良性前列腺增生症（BPH）的病因仍然不确定。 然而，迄今为止，分子遗传学的强大工具尚未被广泛用于研究 这些机制。特别地，遗传关联是鉴定基因和/或遗传标记的有力方法。 赋予疾病易感性的基因座。我们小组和其他人的家庭和双胞胎研究提供了强有力的证据， 有证据表明遗传学是BPH发展的重要因素。这些有趣的发现， 对BPH的遗传易感性表明基因组中存在生殖系序列变异 易患此病我们认为有足够的证据表明， 为了证明系统搜索以鉴定BPH易感性等位基因，以及全基因组研究进展 关联技术使得这样的搜索非常容易产生有价值的结果。单核苷酸 多态性（SNPs）可能与BPH风险直接相关或间接相关 通过与因果序列变异的连锁不平衡（LD）。这些风险相关的SNP将具有 不同的基因型频率之间的男性或没有BPH，可以检测到使用遗传 协会研究。 我们建议检验假设，即通常发生的遗传变异存在于人群中， 与前列腺增生的风险增加有关。本研究的目的是识别和描述这些BPH 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， 证实了对患有和不患有BPH的男性的随访分析。一旦确定，这些位点将提供基础 用于功能研究以表征这些位点在BPH发展中的作用。了解 这种疾病的分子病因学将在开发新的治疗方法方面具有重要的临床意义。 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.