Identification of a novel common genetic risk factor for lumbar disk disease
Identification of a novel common genetic risk factor for lumbar disk disease
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DOI：
10.1001/jama.285.14.1843
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发表时间：
2001-04-11
影响因子：
120.7
通讯作者：
Ala-Kokko, L
中科院分区：
文献类型：
--
作者：
Paassilta, P;Lohiniva, J;Ala-Kokko, L
背景腰椎间盘疾病（LDD）是最常见的肌肉骨骼疾病之一，患病率约为5%，最近在COL 9A 2基因中发现了色氨酸（Trp）等位基因（Trp 2），该等位基因与显性遗传的LDD相关，但仅存在于约4%的人中。目的确定其他IX型胶原基因序列变异是否在LDD的发病机制中发挥作用。病例对照研究于1997年2月至1998年5月在芬兰的大学医院进行。（通过临床和磁共振成像或计算机断层扫描进行评估）和321例无LDD的对照组（186名健康个体，83名原发性骨关节炎患者，31名类风湿性关节炎患者，主要结果测量覆盖胶原IX基因COL 9A 1、COL 9A 2和COL 9A 3的整个编码序列和外显子边界的序列变异频率，所述基因编码蛋白质的α 1、α 2和α 3链，结果3个IX型胶原基因的突变分析均发现α 3链上存在Arg 103-> Trp（精氨酸->色氨酸）突变（Trp 3等位基因）。在LDD病例中，Trp 3等位基因的频率为12.2%，排除了先前鉴定的α 2链中Gln 326-> Trp（谷氨酰胺->色氨酸）取代（Trp 2等位基因）的7名携带者，对照组中为4.7%。频率差异具有统计学意义（P = .000013）。至少1个Trp 3等位基因的存在会增加LDD的风险约3-fold.Conclusion这项研究导致了一种新的常见的遗传危险因素的LDD的鉴定，证实遗传危险因素可能在LDD中发挥重要作用。
Context Lumbar disk disease (LDD) is one of the most common musculoskeletal diseases, with a prevalence of about 5%, A tryptophan (Trp) allele (Trp2) was recently discovered in the COL9A2 gene that is associated with dominantly inherited LDD but is only present in about 4% of Finnish patients with LDD.Objective To determine if other collagen IX gene sequence variations play a role in the pathogenesis of LDD.Design and Setting Case-control study conducted from February 1997 to May 1998 at university hospitals in Finland.Participants A total of 171 individuals with LDD (evaluated clinically and by magnetic resonance imaging or computed tomography) and 321 controls without LDD (186 healthy individuals, 83 patients with primary osteoarthritis, 31 with rheumatoid arthritis, and 21 with chondrodysplasias).Main Outcome Measures Frequencies of sequence variations covering the entire coding sequences and exon boundaries of the collagen IX genes, COL9A1, COL9A2, and COL9A3, which code for the alpha1, alpha2, and alpha3 chains of the protein, detected by conformation-sensitive gel electrophoresis and confirmed by sequencing, compared between individuals with and without LDD,Results Mutation analysis of all 3 collagen IX genes resulted in identification of an Arg103 --> Trp (arginine --> tryptophan) substitution in the alpha3 chain (Trp3 allele). The frequency of the Trp3 allele was 12.2% in LDD cases, excluding 7 individuals who were carriers of the previously identified Gln326 --> Trp (glutamine --> tryptophan) substitution in the a2 chain (Trp2 allele), and was 4.7% among controls. The difference in the frequency was statistically significant (P = .000013). Presence of at least 1 Trp3 allele increases risk of LDD about 3-fold.Conclusion This study led to the identification of a novel common genetic risk factor for LDD, confirming that genetic risk factors likely play a significant role in LDD.