Noponen-Hietala Noora, Virtanen Iita, Karttunen Riitta, Schwenke Susanne, Jakkula Eveliina, Li Hong, Merikivi Riitta, Barral Sandra, Ott Jürg, Karppinen Jaro, Ala-Kokko Leena
Collagen Research Unit, Biocenter and Department of Medical Biochemistry and Molecular Biology, University of Oulu, Aapistie 5A, 90220 Oulu, Finland.
Pain. 2005 Mar;114(1-2):186-94. doi: 10.1016/j.pain.2004.12.015. Epub 2005 Jan 22.
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.
以坐骨神经痛为特征的椎间盘疾病（IDD）是一种常见疾病，约5%的人受其影响。环境因素可能诱发这种疾病，但IDD具有很强的遗传背景。最近的证据表明，炎症是IDD病因的关键因素之一。在此，研究了炎症介质基因在155例与IDD相关的坐骨神经痛患者和179例对照中的可能作用。对48例患者的IL1A、IL1B、IL6和TNFA基因进行了突变分析，并对所有受试者的10个候选细胞因子基因（IL1A、IL1B、IL1RN、TNFA、IL2、IL4、IL4R、IL6、IL10、IFNG）中的16个多态性进行了基因分型。在IL1A、IL1B、IL6或TNFA中未发现致病突变。然而，两组之间IL6基因单核苷酸多态性（SNP）、外显子5中的T15A等位基因频率存在显著差异（P=0.007）。此外，外显子5 SNP的AA和AT基因型在患者中更为常见（P=0.011；比值比[OR]=4.4，95%可信区间[CI]=1.2-15.7；归因风险[AR]=7.5%，1.6-13.1%）。随后对IL6的4个SNP，即外显子5中的G-597A、G-572C、G-174C和T15A生成了单倍型。单倍型GGGA在患者中更为常见（P=0.011；OR=4.8，95%CI=1.6-14.5）。为评估归因风险，为个体分配了单倍型对。GGGA/GGGA或GGGA/其他基因型的存在，其OR为5.4（95%CI=1.5-19.2）。GGGA与疾病的关联高度显著（P=0.0033），相关AR为6.8%（1.9-11.5%）。这些发现支持IL-6基因变异在椎间盘源性疼痛中的作用。
