Division of Urology, Department of Surgery, NorthShore University Health System, Evanston, Illinois, USA.
J Urol. 2013 Mar;189(3):845-8. doi: 10.1016/j.juro.2012.11.044. Epub 2012 Nov 13.
While a clear heritable component underlies lower urinary tract symptoms and benign prostatic hyperplasia, few studies have identified specific genetic factors. In contrast, recent genome-wide association studies identified single nucleotide polymorphisms that increase prostate cancer risk. Some of these single nucleotide polymorphisms may also predispose to surgical intervention for benign prostatic hyperplasia. We determined whether these single nucleotide polymorphisms are also associated with lower urinary tract symptom severity and benign prostatic hyperplasia medication use.
The genotypes of 38 single nucleotide polymorphisms previously associated with prostate cancer risk were determined for 1,168 healthy white male volunteers. American Urological Association symptom index score and medication for benign prostatic hyperplasia were documented prospectively. Statistical analyses were done to compare the frequency of the single nucleotide polymorphisms with American Urological Association symptom index and benign prostatic hyperplasia medication use.
Several single nucleotide polymorphisms, including rs2736098 on chromosome 5p15, showed a significant relationship with benign prostatic hyperplasia medication. After adjusting for the other genetic variants, patient age and medication use, rs1571801 on chromosome 9q33.2 (OR 1.31, 95% CI 1.0-1.74) and rs5945572 on chromosome Xp11 (OR 1.28, 95% CI 1.04-1.59) were significantly associated with increased urinary symptoms. In contrast, rs445114 on chromosome 8q24 was marginally associated with decreased urinary symptoms (OR 0.83, 95% CI 0.66-1.01).
Of 38 single nucleotide polymorphisms that predispose to prostate cancer we identified 3 that are also associated with a well characterized lower urinary tract symptom phenotype. These single nucleotide polymorphisms may aid in the improved characterization of men with lower urinary tract symptoms/benign prostatic hyperplasia.
尽管下尿路症状和良性前列腺增生的发生有明显的遗传因素，但很少有研究确定具体的遗传因素。相比之下，最近的全基因组关联研究确定了增加前列腺癌风险的单核苷酸多态性。其中一些单核苷酸多态性也可能导致良性前列腺增生的手术干预。我们确定这些单核苷酸多态性是否也与下尿路症状严重程度和良性前列腺增生药物治疗有关。
对 1168 名健康白种男性志愿者的 38 种先前与前列腺癌风险相关的单核苷酸多态性的基因型进行了测定。前瞻性记录美国泌尿外科学会症状指数评分和用于治疗良性前列腺增生的药物。进行了统计学分析，以比较单核苷酸多态性与美国泌尿外科学会症状指数和良性前列腺增生药物治疗的频率。
包括染色体 5p15 上的 rs2736098 在内的几种单核苷酸多态性与良性前列腺增生药物治疗有显著关系。在调整了其他遗传变异、患者年龄和药物使用后，染色体 9q33.2 上的 rs1571801（OR 1.31，95%CI 1.0-1.74）和染色体 Xp11 上的 rs5945572（OR 1.28，95%CI 1.04-1.59）与增加的尿症状显著相关。相反，染色体 8q24 上的 rs445114 与减少的尿症状呈边缘相关（OR 0.83，95%CI 0.66-1.01）。
在导致前列腺癌的 38 种单核苷酸多态性中，我们确定了 3 种与明确的下尿路症状表型也有关联的单核苷酸多态性。这些单核苷酸多态性可能有助于改善对有下尿路症状/良性前列腺增生的男性的特征描述。
