Do HOXB9 and COL1A1 genes play a role in congenital dislocation of the hip? Study in a Caucasian population
Do HOXB9 and COL1A1 genes play a role in congenital dislocation of the hip? Study in a Caucasian population
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DOI：
10.1016/j.joca.2008.12.012
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发表时间：
2009-08-01
影响因子：
7
通讯作者：
Ferec, C.
中科院分区：
文献类型：
--
作者：
Rouault, K.;Scotet, V.;Ferec, C.
目的：先天性髋关节脱位（CDH）是最常见的先天性骨骼疾病之一，其对应于股骨头在髋臼中的异常就位。通常认为CDH存在遗传成分。然而，人们对所涉及的遗传因素知之甚少。本研究旨在确定17号染色体上两个潜在的候选基因在CDH中的作用：HOXB 9（参与肢体胚胎发育）和COL1A1（参与关节松弛）。我们在CDH特别常见的布列塔尼西部（法国）建立了一项病例对照关联研究（239例病例和239例对照）。使用Tagger选择每个基因中的信息性单核苷酸多态性（SNP）组，并使用SNaPshot（R）方法进行基因分型（分别为n = 2和n = 10）。使用SAS和Haploview软件，通过单位点和基于单倍型的分析来检验关联。此外，我们对来自81个三人组的样本的相同多态性进行了传递不平衡检验（TDT）（即，结果：病例对照研究结果显示，HOXB 9和COL1A1中的tagSNPs与CDH无显著相关性。此外，TDT并没有揭示失真的等位基因和单倍型transmittance的研究markers.Conclusion：我们的研究不支持HOXB 9和COL1A1和CDH在我们的人口之间的关联。这些阴性结果是通过基于人群和家庭的设计获得的。CDH的遗传成分的分析应集中在其他候选基因。(C)2009年国际骨关节炎研究学会。由爱思唯尔有限公司发布。保留所有权利。
Objective: 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).Method. 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 (R) 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).Results: 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.Conclusion: 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. (C) 2009 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.