Department of Plastic Surgery, University Medical Center Groningen and University of Groningen, Groningen, the Netherlands.
J Sex Med. 2012 May;9(5):1430-4. doi: 10.1111/j.1743-6109.2012.02704.x. Epub 2012 Apr 10.
Peyronie's disease (PD) is a fibromatosis of the penis, with a pathology very similar to what is seen in the hand (palmar fascia) in Dupuytren's disease (DD). Recently, we performed a genome-wide association study and identified nine genetic loci containing common variants associated with DD. Seven of these loci mapped within or near genes of the canonical WNT pathway and each locus yielded relatively large odds ratios (ORs) for DD disease status.
Given the clinical overlap between PD and DD, we examined whether the nine DD susceptibility loci are also involved in PD.
An association study was performed using a case/control design. From 2007 to 2010, we prospectively included 111 men who had been clinically diagnosed with PD. Control subjects (N = 490 males) were randomly drawn from a population-based cohort from the same region of the Netherlands. Allele frequencies in the 111 PD cases and 490 controls were compared using a 1-degree-of-freedom basic chi-square test. A P value < 0.05 after Bonferroni correction for the nine tested single nucleotide polymorphisms (SNPs) was considered statistically significant (i.e., P < 0.0056).
Association of genetic markers (SNPs) with PD.
We observed significant association with SNP rs4730775 at the wingless-type MMTV integration site family member 2 (WNT2) locus on chromosome 7 (P = 0.0015, OR 0.61), but found no evidence for the other eight loci being involved with PD despite the large effect size seen for some of these variants in DD. The WNT2 association was even more significant after we removed 15 patients with comorbid DD.
WNT2 is a susceptibility locus for PD and our finding provides evidence for a partly shared genetic susceptibility between PD and DD.
佩罗尼氏病（PD）是一种阴茎纤维瘤病，其病理学与掌腱膜挛缩症（DD）中所见的非常相似。最近，我们进行了全基因组关联研究，确定了九个包含与 DD 相关的常见变异体的遗传位点。这七个位点位于经典 WNT 途径的基因内或附近，每个位点产生的 DD 疾病状态的相对较大优势比（OR）。
鉴于 PD 和 DD 之间存在临床重叠，我们检查了九个 DD 易感性位点是否也与 PD 有关。
使用病例对照设计进行关联研究。2007 年至 2010 年，我们前瞻性纳入了 111 名临床诊断为 PD 的男性患者。对照受试者（N=490 名男性）是从荷兰同一地区的人群队列中随机抽取的。使用 1 度自由度基本卡方检验比较 111 例 PD 病例和 490 例对照的等位基因频率。在对 9 个测试的单核苷酸多态性（SNP）进行 Bonferroni 校正后，P 值<0.05 被认为具有统计学意义（即 P<0.0056）。
遗传标记（SNP）与 PD 的关联。
我们观察到在 7 号染色体上的无翅型 MMTV 整合位点家族成员 2（WNT2）基因座的 SNP rs4730775 与 PD 显著相关（P=0.0015，OR 0.61），但尽管这些变异在 DD 中存在较大的效应量，仍没有证据表明其他八个位点与 PD 有关。在我们去除 15 名合并 DD 的患者后，WNT2 关联更加显著。
WNT2 是 PD 的易感基因，我们的发现为 PD 和 DD 之间存在部分共同的遗传易感性提供了证据。
