Balbi G, Ferrera F, Rizzi M, Piccioli P, Morabito A, Cardamone L, Ghio M, Palmisano G L, Carrara P, Pedemonte S, Sessarego M, De Angioletti M, Notaro R, Indiveri F, Pistillo M P
Department of Oncology, Biology and Genetics, University of Genoa, Genoa, Italy.
Clin Exp Immunol. 2007 Jul;149(1):40-7. doi: 10.1111/j.1365-2249.2007.03394.x. Epub 2007 Apr 25.
Systemic sclerosis (SSc) is a complex and heterogeneous autoimmune disorder with a multi-factorial pathogenesis. Like other autoimmune disorders, the possible role of specific cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphisms in predisposing to SSc has been hypothesized, but it remains controversial. CTLA-4 promoter (-318C/T) and exon 1 (+49 A/G) polymorphisms have been analysed in 43 Italian females with SSc and in 93 unrelated matched healthy controls by a newly designed tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) method. No significant association has been found with either polymorphisms.Nevertheless, SSc patients without concomitant Hashimoto's thyroiditis (HT) were carrying both the -318T allele (P = 0.031) and the +49 G allele (P = 0.076) more frequently than SSc patients with HT [defined by positivity for anti-thyroperoxidase (TPO) and anti-thyroglobulin (TGA) autoantibodies] than controls. Haplotype analysis confirms this association (P = 0.028), and suggests the predominant role of the -318T, whereas that of the +49 G, if any, seems weak. Thus, in Italian SSc patients the CTLA-4 -318C/T promoter polymorphism appears to be associated with the susceptibility to develop SSc without thyroid involvement. Larger studies are needed to confirm these findings and to clarify whether the -318C/T polymorphism is the functional responsible or whether it reflects the presence of another linked genetic element in the same chromosomal region.
系统性硬化症（SSc）是一种复杂的异质性自身免疫性疾病，其发病机制具有多因素性。与其他自身免疫性疾病一样，特定细胞毒性T淋巴细胞抗原4（CTLA-4）基因多态性在SSc易感性中的可能作用已被提出假说，但仍存在争议。采用新设计的四引物扩增阻滞突变系统-聚合酶链反应（T-ARMS-PCR）方法，对43例意大利女性SSc患者和93例无亲缘关系的匹配健康对照者进行了CTLA-4启动子（-318C/T）和外显子1（+49 A/G）多态性分析。未发现与任何一种多态性有显著关联。然而，不伴有桥本甲状腺炎（HT）的SSc患者携带-318T等位基因（P = 0.031）和+49 G等位基因（P = 0.076）的频率高于伴有HT的SSc患者[由抗甲状腺过氧化物酶（TPO）和抗甲状腺球蛋白（TGA）自身抗体阳性定义]和对照者。单倍型分析证实了这种关联（P = 0.028），并提示-318T起主要作用，而+49 G（如果有作用的话）似乎作用较弱。因此，在意大利SSc患者中，CTLA-4 -318C/T启动子多态性似乎与无甲状腺受累的SSc易感性相关。需要更大规模的研究来证实这些发现，并阐明-318C/T多态性是否是功能性原因，或者它是否反映了同一染色体区域中另一个连锁遗传元件的存在。
