Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
Mol Pain. 2012 Sep 24;8:72. doi: 10.1186/1744-8069-8-72.
Mutations in SCN9A, encoding the alpha subunit of the voltage-gated sodium channel (Nav1.7), have caused severe pain disorders and congenital insensitivity to pain. The aim of this study was to validate the previously reported association between a common non-synonymous polymorphism (R1150W, rs6746030) in SCN9A and chronic widespread pain (CWP), in independent population-based cohorts.
Genotype data for rs6746030 was available in four population-based cohorts (EPIFUND, the European Male Ageing Study (EMAS), the Framingham study and the Dyne Steel DNA Bank of Ageing and Cognition). Pain was assessed using body manikins and CWP was scored using American College of Rheumatology (ACR) criteria in all cohorts, except the Framingham study which assessed widespread pain (WP) using ACR criteria on a joint pain homunculus. Controls were subjects who reported no pain. Logistic regression (additive genetic model) was used to test for association between rs6746030 and CWP compared to controls, adjusting for study centre in EMAS. Generalised estimating equation regression was used to test for association between rs6746030 and WP, whilst accounting for relatedness between subjects in the Framingham study.Genotype data for rs6746030 was available for 1071 CWP cases and 3212 controls. There was no significant association between CWP and rs6476030 in individual cohorts or when combined in a fixed-effects meta-analysis (Odds Ratio = 0.96 (95% confidence interval 0.82, 1.11) p = 0.567).
In contrast to a previous study, no association between a non-synonymous polymorphism in SCN9A and CWP was observed in multiple population-based cohorts.
SCN9A 基因突变,编码电压门控钠离子通道(Nav1.7)的α亚基,引起严重疼痛障碍和先天性疼痛感觉缺失。本研究的目的是在独立的基于人群的队列中验证先前报道的 SCN9A 中常见的非同义多态性(R1150W,rs6746030)与慢性广泛性疼痛(CWP)之间的关联。
四个基于人群的队列(EPIFUND、欧洲男性衰老研究(EMAS)、弗雷明汉研究和 Dyne Steel 年龄与认知 DNA 银行)中提供了 rs6746030 的基因型数据。在所有队列中,使用身体模型评估疼痛,并且除了弗雷明汉研究之外,使用 ACR 标准对 CWP 进行评分,该研究使用关节疼痛小人图上的 ACR 标准评估广泛疼痛(WP)。对照是报告无疼痛的受试者。使用 logistic 回归(加性遗传模型)来测试与 rs6746030 相比,与对照组相比,CWP 与 rs6746030 之间的关联,在 EMAS 中调整研究中心。使用广义估计方程回归来测试与 rs6746030 之间的关联,同时考虑到弗雷明汉研究中受试者之间的相关性。rs6746030 的基因型数据可用于 1071 例 CWP 病例和 3212 例对照。在个体队列或在固定效应荟萃分析中组合时,CWP 与 rs6476030 之间没有显著关联(优势比=0.96(95%置信区间 0.82,1.11),p=0.567)。
与先前的研究相比,在多个基于人群的队列中,SCN9A 中的非同义多态性与 CWP 之间没有关联。