Further insights into the role of T222P variant of RXFP2 in non-syndromic cryptorchidism in two Mediterranean populations
Further insights into the role of T222P variant of RXFP2 in non-syndromic cryptorchidism in two Mediterranean populations
复制标题
DOI：
10.1111/j.1365-2605.2010.01088.x
复制
发表时间：
2011-08-01
影响因子：
--
通讯作者：
Krausz, C.
中科院分区：
文献类型：
--
作者：
Ars, E.;Lo Giacco, D.;Krausz, C.
孤立性隐睾的发病机制仍在很大程度上不明。睾丸发育不良最相关的候选基因的突变筛查导致文献中有争议的数据。特别是，RXFP 2基因的T222 P遗传变体的作用仍然存在争议。鉴于这些争议，本研究的目的是提供关于两个地中海人群中这种遗传变异的进一步数据。共分析了来自西班牙的577例受试者和来自意大利的550例受试者（有和无隐睾病史）。在单侧和双侧病例以及12例对照中均发现T222 P替代。这些数据排除了T222 P变异和睾丸发育不良之间明确的因果关系。在西班牙人群中，T222 P变异在病例组和对照组中的频率相似，而在意大利，隐睾组中T222 P的频率显著较高（p = 0.031）。这两个国家之间观察到的差异和T222 P变异体的高度可变表型表达可能取决于遗传背景或环境条件。T222 P携带者及其父母的RXFP 2基因的单倍型分析表明，该变异与先前推断的C-C-G-A-13单倍型有关，因此进一步支持了“奠基者效应”假说。总之，我们的数据表明，T222 P是一种常见的变异，在西班牙人口没有致病作用。虽然在意大利，它似乎赋予一个轻微的风险（比值比= 3.17，95%置信区间：1.07-9.34）隐睾，筛查这种变异的诊断目的是不建议，因为相对较高的频率控制载体（1.4%的意大利男性无隐睾病史）。
The aetiopathogenesis of isolated cryptorchidism remains largely unknown. Mutation screenings in the most relevant candidate genes for testicular maldescent lead to controversial data in the literature. In particular, the role of the T222P genetic variant of the RXFP2 gene is still debated. Given the controversies, the aim of this study was to provide further data on this genetic variant in two Mediterranean populations. A total of 577 subjects from Spain and 550 from Italy (with and without a history of cryptorchidism) were analysed. The T222P substitution was found in both unilateral and bilateral cases and in a total of 12 controls. These data exclude a clear-cut cause-effect relationship between T222P variant and testicular maldescent. The T222P variant was found at a similar frequency in both cases and controls in the Spanish population, whereas in Italy, the frequency of T222P resulted significantly higher in the cryptorchid group (p = 0.031). The observed difference between the two countries and the highly variable phenotypic expression of the T222P variant may depend on the genetic background or on environmental conditions. The haplotype analysis of the RXFP2 gene in T222P carriers and their parents showed that this variant is linked to the previously inferred C-C-G-A-13 haplotype and consequently provides further support to the 'founder effect' hypothesis. In conclusion, our data indicate that T222P is a frequent variant in the Spanish population with no pathogenic effect. Although in Italy it seems to confer a mild risk (odds ratio = 3.17, 95% confidence interval: 1.07-9.34) to cryptorchidism, the screening for this variant for diagnostic purposes is not advised because of the relatively high frequency of control carriers (1.4% of Italian men without a history of cryptorchidism).