Inserm, U613, Univ Brest, UMR-S613, Brest F-29200, France.
Osteoarthritis Cartilage. 2009 Aug;17(8):1099-105. doi: 10.1016/j.joca.2008.12.012. Epub 2009 Mar 24.
Congenital dislocation of the hip (CDH), which is one of the most common congenital skeletal disorders, corresponds to an abnormal seating of the femoral head in the acetabulum. It is commonly admitted that CDH presents a genetic component. However, little is known about the genetic factors involved. This study aimed to determine the role of two potential candidate genes on chromosome 17 in CDH: HOXB9 (involved in limb embryonic development) and COL1A1 (involved in joint laxity).
We set up a case-control association study (239 cases and 239 controls) in western Brittany (France) where CDH is particularly frequent. The set of informative single nucleotide polymorphisms (SNPs) in each gene was selected using Tagger and genotyped using the SNaPshot method (n=2 and n=10, respectively). The association was tested both through single-locus and haplotype-based analyses, using SAS and Haploview softwares. In addition, we carried out the transmission disequilibrium test (TDT) with the same polymorphisms from a sample of 81 trios (i.e., 81 patients included in the case-control study and their both parents).
The case-control study revealed no significant association between CDH and the tagSNPs selected in both HOXB9 and COL1A1. Moreover, the TDT did not reveal distortion in allelic and haplotype transmission of the studied markers.
Our study did not support an association between HOXB9 and COL1A1 and CDH in our population. These negative findings were obtained by population- and family-based designs. Analysis of the genetic component of CDH should focus on other candidate genes.
先天性髋关节脱位（CDH）是最常见的先天性骨骼疾病之一，其特征是股骨头在髋臼内的异常位置。人们普遍认为 CDH 具有遗传成分。然而，目前对于涉及的遗传因素知之甚少。本研究旨在确定染色体 17 上两个潜在候选基因 HOXB9（参与肢体胚胎发育）和 COL1A1（参与关节松弛）在 CDH 中的作用。
我们在布列塔尼西部（法国）建立了一个病例对照关联研究（239 例病例和 239 例对照），该地区 CDH 发病率特别高。使用 Tagger 选择每个基因中的信息单核苷酸多态性（SNP），并使用 SNaPshot 方法进行基因分型（分别为 n=2 和 n=10）。使用 SAS 和 Haploview 软件通过单基因座和单倍型分析测试关联。此外，我们还使用来自 81 个三体型（即 81 例包含在病例对照研究中的患者及其双亲）的相同多态性进行传递不平衡测试（TDT）。
病例对照研究表明，HOXB9 和 COL1A1 中选择的标记 SNP 与 CDH 之间没有显著关联。此外，TDT 并未显示研究标记的等位基因和单倍型传递失真。
我们的研究在我们的人群中不支持 HOXB9 和 COL1A1 与 CDH 之间的关联。这些阴性发现是通过基于人群和基于家庭的设计获得的。CDH 的遗传成分分析应集中在其他候选基因上。
