Hu Y, Li L, Seidelmann S B, Timur A A, Shen P H, Driscoll D J, Wang Q K
Center for Cardiovascular Genetics, Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Ann Hum Genet. 2008 Sep;72(Pt 5):636-43. doi: 10.1111/j.1469-1809.2008.00458.x. Epub 2008 Jun 16.
Klippel-Trenaunay syndrome (KTS) is a severe congenital disorder characterized by capillary malformations, venous malformations or varicose veins, and hypertrophy of the affected tissues. The angiogenic factor gene AGGF1 was previously identified as a candidate susceptibility gene for KTS, but further genetic studies are needed to firmly establish the genetic relationship between AGGF1 and KTS. We analyzed HapMap data and identified two tagSNPs, rs13155212 and rs7704267 that capture information for all common variants in AGGF1. The two SNPs were genotyped in 173 Caucasian KTS patients and 477 Caucasian non-KTS controls, and both significantly associated with susceptibility for KTS (P= 0.004 and 0.013, respectively). Permutation testing also showed a significant empirical P value for the association (empirical P= 0.006 and 0.015, respectively). To control for potential confounding due to population stratification, the population structure for both cases and controls was characterized by genotyping of 38 ancestry-informative markers (AIMs) and the STRUCTURE program. The association between the AGGF1 SNPs and KTS remained significant after multivariate analysis by incorporating the inferred cluster scores as a covariate or after removal of outlier individuals identified by STRUCTURE. These results suggest that common AGGF1 variants confer risk of KTS.
克-特综合征（KTS）是一种严重的先天性疾病，其特征为毛细血管畸形、静脉畸形或静脉曲张，以及受累组织的肥大。血管生成因子基因AGGF1先前被确定为KTS的候选易感基因，但需要进一步的遗传学研究来牢固确立AGGF1与KTS之间的遗传关系。我们分析了HapMap数据，并鉴定出两个标签单核苷酸多态性（tagSNP），即rs13155212和rs7704267，它们捕获了AGGF1中所有常见变异的信息。对173例白种人KTS患者和477例白种人非KTS对照进行了这两个SNP的基因分型，二者均与KTS易感性显著相关（P值分别为0.004和0.013）。置换检验也显示该关联具有显著的经验性P值（经验性P值分别为0.006和0.015）。为控制由于人群分层导致的潜在混杂因素，通过对38个祖先信息标记（AIM）进行基因分型和使用STRUCTURE程序对病例组和对照组的人群结构进行了表征。在将推断的聚类分数作为协变量纳入多变量分析后，或者在去除由STRUCTURE鉴定出的异常个体后，AGGF1 SNP与KTS之间的关联仍然显著。这些结果表明，AGGF普通变异会增加患KTS的风险。
