Mangold Elisabeth, Reutter Heiko, León-Cachón Rafael B R, Ludwig Kerstin U, Herms Stefan, Chacón-Camacho Óscar, Ortiz-López Rocío, Paredes-Zenteno Mario, Arizpe-Cantú Abelardo, Muñoz-Jiménez Sergio G, Nowak Stefanie, Kramer Franz-Josef, Wienker Thomas F, Nöthen Markus M, Knapp Michael, Rojas-Martínez Augusto
Institute of Human Genetics, University of Bonn, Bonn, Germany.
Eur J Oral Sci. 2012 Oct;120(5):373-7. doi: 10.1111/j.1600-0722.2012.00991.x. Epub 2012 Aug 24.
Non-syndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common of all congenital malformations and has a multifactorial etiology. Findings in mice suggest that the v-ski sarcoma viral oncogene homolog (SKI) gene is a candidate gene for orofacial clefting. In humans, a significant association between rs2843159 within SKI and NSCL/P has been reported in patients from the Philippines and South America. In the South American patients, the association was driven by the subgroup of patients with non-syndromic cleft lip only (NSCLO). Here we investigated the association with rs2843159 in a Mayan Mesoamerican population (172 NSCL/P patients and 366 controls). In addition, we analyzed the phenotypic subgroups NSCLO and non-syndromic cleft of lip and palate (NSCLP). A trend towards association between rs2843159 and NSCL/P was observed in the Mayan cohort (P = 0.097), and we found a stronger association in the NSCLP subgroup (P = 0.072) despite a limited sample size. To investigate whether other common variants within the SKI gene contribute to NSCL/P susceptibility in European and Asian populations, we also analyzed genotypic data from two recent genome-wide association studies using set-based statistical approaches. These analyses detected a trend toward association in the European population. Our data provide limited support for the hypothesis that common SKI variants are susceptibility factors for NSCL/P.
非综合征性唇裂伴或不伴腭裂（NSCL/P）是所有先天性畸形中最常见的一种，其病因是多因素的。小鼠研究结果表明，v-ski肉瘤病毒癌基因同源物（SKI）基因是口面部裂隙的候选基因。在人类中，菲律宾和南美洲的患者报告称SKI基因内的rs2843159与NSCL/P之间存在显著关联。在南美洲患者中，这种关联是由仅患有非综合征性唇裂（NSCLO）的患者亚组驱动的。在此，我们调查了玛雅中美洲人群（172例NSCL/P患者和366例对照）中rs2843159的关联情况。此外，我们分析了NSCLO和非综合征性唇腭裂（NSCLP）的表型亚组。在玛雅队列中观察到rs2843159与NSCL/P之间存在关联趋势（P = 0.097），尽管样本量有限，但我们在NSCLP亚组中发现了更强的关联（P = 0.072）。为了研究SKI基因内的其他常见变异是否会导致欧洲和亚洲人群对NSCL/P易感，我们还使用基于集合的统计方法分析了两项近期全基因组关联研究的基因型数据。这些分析在欧洲人群中检测到了关联趋势。我们的数据为常见SKI变异是NSCL/P易感因素这一假设提供了有限的支持。
