Ramasawmy Rajendranath, Faé Kellen C, Spina Guilherme, Victora Gabriel D, Tanaka Ana Cristina, Palácios Selma A, Hounie Ana G, Miguel Euripides C, Oshiro Sandra E, Goldberg Anna C, Kalil Jorge, Guilherme Luiza
Heart Institute (InCor), School of Medicine, University of Sao Paulo, Brazil.
Mol Immunol. 2007 Mar;44(8):1873-8. doi: 10.1016/j.molimm.2006.10.001. Epub 2006 Oct 31.
Rheumatic fever (RF)/rheumatic heart disease (RHD) is an inflammatory disease with a complex etiology in which Group A streptococci within a genetically susceptible host untreated for strep-throat may deviate the innate and adaptive arms of the immune system towards recognition of autoantigens. The TNFA gene has been associated with a number of autoimmune diseases, including RF. We investigated whether the G-308A and G-238A polymorphisms of the TNFA gene are associated with clinical outcomes of RF in a cohort of 318 patients and 281 healthy controls (HC). Both polymorphisms showed borderline associations with RF (TNFA -308G/A, OR=1.4 [1-2.2], P=0.026; TNFA -238G/A, OR=1.9 [1-3.3], P=0.015). The presence of either one of the minor alleles (-308A and -238A) was more common among patients with RF/RHD than controls (P=0.0006). Stratification of patients according to clinical phenotype also showed significant associations between presence of either one of the minor alleles and RHD (Pc=0.0006) when compared with controls. This association was stronger with the development of aortic valve lesions. In contrast, there was no association between genotype and Sydenham's chorea or RF patients with mild carditis. In conclusion, we show that the TNFA is a susceptibility locus for RF. The ability to predict which RF patients will develop valve lesion may have therapeutic, economic and social implications.
风湿热（RF）/风湿性心脏病（RHD）是一种病因复杂的炎症性疾病，在遗传易感宿主中，未经治疗的A组链球菌性咽喉炎可能会使免疫系统的固有免疫和适应性免疫偏离对自身抗原的识别。肿瘤坏死因子α（TNFA）基因与包括RF在内的多种自身免疫性疾病相关。我们在一个由318例患者和281例健康对照（HC）组成的队列中，研究了TNFA基因的G-308A和G-238A多态性是否与RF的临床结局相关。两种多态性均显示出与RF的临界相关性（TNFA -308G/A，比值比[OR]=1.4[1-2.2]，P=0.026；TNFA -238G/A，OR=1.9[1-3.3]，P=0.015）。RF/RHD患者中次要等位基因（-308A和-238A）之一的存在比对照组更常见（P=0.0006）。根据临床表型对患者进行分层后发现，与对照组相比，次要等位基因之一的存在与RHD之间也存在显著相关性（Pc=0.0006）。这种相关性在主动脉瓣病变的发生中更强。相比之下，基因型与 Sydenham 舞蹈病或轻度心肌炎的RF患者之间没有关联。总之，我们表明TNFA是RF的一个易感基因座。预测哪些RF患者会发生瓣膜病变的能力可能具有治疗、经济和社会意义。
