Oregón-Romero Edith, Vázquez-Del Mercado Mónica, Ruiz-Quezada Sandra Luz, Navarro-Hernández Rosa Elena, Rangel-Villalobos Héctor, Martínez-Bonilla Gloria, Bernard-Medina Ana Guilaisne, Armendáriz-Borunda Juan, García-Bañuelos Jesús, Muñoz-Valle José Francisco
Instituto de Investigación en Reumatología y del Sistema Músculo Esquelético, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, México.
J Investig Med. 2008 Oct;56(7):937-43. doi: 10.2310/JIM.0b013e318189152b.
Rheumatoid arthritis (RA) is characterized by a progressive joint damage mediated mainly by tumor necrosis factor alpha (TNFalpha). We investigated the relationship of TNFalpha-308 and -238 polymorphisms with messenger RNA (mRNA) expression and soluble TNFalpha (sTNFalpha) in 50 RA and 100 healthy subjects (HS).
Clinical and laboratory assessments were performed. Spanish Health Assessment Questionnaire Disability Index, Spanish version of Arthritis Impact Measurement Scales and Disease Activity Score using 28 joint count indices were applied to RA patients. The TNFalpha-308 and -238 polymorphisms were performed by polymerase chain reaction and restriction fragment length polymorphism techniques. The mRNA expression of TNFalpha was quantified by real-time polymerase chain reaction. The sTNFalpha levels were measured by enzyme-linked immunosorbent assay.
The TNFalpha-308 polymorphism showed an increased frequency of guanine (G)/adenine (A) genotype in RA versus HS (P = 0.03; 95% confidence interval, 1.05-8.08; odds ratio, 2.9) and also the A allele was more frequent in RA patients versus HS (P = 0.04; 95% confidence interval, 1.01-7.29; odds ratio, 2.7). The G/G genotype and also the G allele were more frequent in HS. No significant difference was observed in TNFalpha-238 polymorphism. Rheumatoid arthritis patients showed high TNFalpha mRNA expression (1.33-fold). The G/G genotype was associated with high mRNA and sTNFalpha levels in both TNFalpha polymorphisms. The correlation of sTNFalpha levels with C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, Spanish Health Assessment Questionnaire Disability Index, and Spanish version of Arthritis Impact Measurement Scales, was observed.
The TNFalpha-308 polymorphism is a susceptibility marker to RA. The G/G genotype is associated with a high mRNA and soluble TNFalpha expression.
类风湿关节炎（RA）的特征是主要由肿瘤坏死因子α（TNFα）介导的进行性关节损伤。我们在50例RA患者和100例健康对照者（HS）中研究了TNFα -308和-238多态性与信使核糖核酸（mRNA）表达及可溶性TNFα（sTNFα）的关系。
进行了临床和实验室评估。对RA患者应用西班牙健康评估问卷残疾指数、西班牙语版关节炎影响测量量表以及采用28个关节计数指标的疾病活动评分。通过聚合酶链反应和限制性片段长度多态性技术检测TNFα -308和-238多态性。采用实时聚合酶链反应定量TNFα的mRNA表达。通过酶联免疫吸附测定法测量sTNFα水平。
与HS相比，RA患者中TNFα -308多态性的鸟嘌呤（G）/腺嘌呤（A）基因型频率增加（P = 0.03；95%置信区间，1.05 - 8.08；比值比，2.9），并且RA患者中A等位基因也比HS更常见（P = 0.04；95%置信区间，1.01 - 7.29；比值比，2.7）。G/G基因型以及G等位基因在HS中更常见。TNFα -238多态性未观察到显著差异。RA患者表现出较高的TNFα mRNA表达（1.33倍）。在两种TNFα多态性中，G/G基因型均与高mRNA和sTNFα水平相关。观察到sTNFα水平与C反应蛋白、红细胞沉降率、类风湿因子、西班牙健康评估问卷残疾指数以及西班牙语版关节炎影响测量量表之间存在相关性。
TNFα -308多态性是RA的易感性标志物。G/G基因型与高mRNA和可溶性TNFα表达相关。
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