Genetic variations in IL6 associate with intervertebral disc disease characterized by sciatica
Genetic variations in IL6 associate with intervertebral disc disease characterized by sciatica
复制标题
DOI：
10.1016/j.pain.2004.12.015
复制
发表时间：
2005-03-01
期刊：
影响因子：
7.4
通讯作者：
Ala-Kokko, L
中科院分区：
文献类型：
--
作者：
Noponen-Hietala, N;Virtanen, L;Ala-Kokko, L
以坐骨神经痛为特征的腰间盘病是一种常见的疾病，约有5%的人受到影响。环境因素是该病的易感因素，但IDD有很强的遗传背景。最近的证据表明，炎症是IDD病因学的关键因素之一。在这里，研究了155名IDD相关性坐骨神经痛患者和179名对照的炎性介质基因的可能作用。对48例患者进行了IL1a、IL1B、IL6和TNFA基因突变分析，并对10个候选细胞因子基因(IL1a、IL1B、IL1RN、TNFA、IL2、IL4、IL4R、IL6、IL10、IFNG)的16个多态性进行了基因分型。未发现IL1a、IL1B、IL6或TNFA的致病突变。但IL 6SNP、T15A外显子5的等位基因频率在两组间差异有统计学意义(P=0.007)。外显子5SNP的AA和AT等位基因在患者中更为常见(P=0.011；OR=4.4，95%CI=1.2~15.7；AR=7.5%，1.6~13.1%)。然后产生了4个IL6 SNP，G-597A，G-572C的单倍型。G-174C和T15A外显子5。单倍型GGGA在患者中更常见(P=0.011；OR=4.895%CI1.6~14.5)。为了评估归因风险，为个体分配了单倍型对。GGGA/GGGA或GGGA/其他基因型的OR值为5.4(95%CI=1.5~19.2)。GGGA与疾病的相关性非常显著(P=0.0033)，AR的相关性为6.8%(1.9-11.5%)。这些发现支持IL-6基因变异在间盘源性疼痛中的作用。(C)2004年国际疼痛研究协会。爱思唯尔出版，版权所有。
Intervertebral disc disease (IDD) characterized by sciatica is a common disorder affecting about 5% of individuals. Environmental factors can predispose to this disease, but IDD has a strong genetic background. Recent evidence suggests that inflammation is one of the key factors in the etiology of IDD. Here, a possible role of the inflammatory mediator genes was studied in 155 patients with IDD-related sciatica and 179 controls. Forty-eight patients were analyzed for mutations in the IL1A, IL1B, IL6 and TNFA genes, and 16 polymorphisms in 10 candidate cytokine genes (IL1A, IL1B, IL1RN, TNFA, IL2, IL4, IL4R, IL6, IL10, IFNG) were genotyped from all subjects. No disease-causing mutations were identified in IL1A, IL1B, IL6 or TNFA. Allele frequencies were, however, significantly different between the two groups for IL6 SNP, T15A in exon 5 (P = 0.007). Furthermore, the genotypes AA and AT of the exon 5 SNP were more common in the patients (P = 0.011; OR = 4.4, 95% CI = 1.2-15.7; AR = 7.5%, 1.6-13.1%). Haplotypes were then generated for four IL6 SNPs, G-597A, G-572C. G-174C,and T15A in exon 5. Haplotype GGGA was more common in the patients (P = 0.011; OR = 4.8, 95% CI 1.6-14.5). To evaluate attributable risk, haplotype pairs were assigned for the individuals. The presence of GGGA/GGGA or GGGA/other genotypes had an OR of 5.4 (95% CI = 1.5-19.2). Association of GGGA with disease was highly significant (P = 0.0033), and the associated AR was 6.8% (1.9-11.5%). These findings support the role of IL-6 genetic variations in discogenic pain. (c) 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.