Consiglio C R, Veit T D, Monticielo O A, Mucenic T, Xavier R M, Brenol J C T, Chies J A B
Genetics Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
Tissue Antigens. 2011 Jun;77(6):540-5. doi: 10.1111/j.1399-0039.2011.01635.x. Epub 2011 Mar 14.
Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease that affects several organs and systems. Its etiology remains unknown, although it is probably multifactorial. The human leukocyte antigen G (HLA-G) is a nonclassic major histocompatibility complex I molecule characterized by restricted expression and low DNA polymorphism. HLA-G plays a role in immunosuppression through different mechanisms. In inflammatory diseases, it has been postulated that HLA-G expression may be a possible mechanism of tissue protection against exacerbated inflammatory response. On the 3' untranslated region (3' UTR) of the HLA-G gene, there is an insertion/deletion polymorphism of 14 bp (rs1704) that was shown to influence the mRNA stability. The influence of this polymorphism in disease susceptibility is controversial. Also in the 3' UTR there is a single nucleotide polymorphism C/G (rs1063320) on the position +3142, at a possible binding site for microRNAs (miRNAs) and having an influence on miRNA affinity. In this study, we analyzed the +3142C>G and the 14 bp polymorphisms in 195 SLE European-derived female patients. Our findings show a significant increase of the +3142G allele frequency among patients as compared with controls (0.58 vs 0.47, P = 0.011). Also, patients presented a higher frequency of the GG genotype (OR = 1.90, 95% CI: 1.08-3.42). Double heterozygotes for the two polymorphisms presented a milder mean systemic lupus erythematosus disease activity index (SLEDAI) than heterozygotes for only one of the variants or non-heterozygous individuals (1.56 vs 3.15 and 3.26, respectively, corrected P = 0.044). These results suggest the involvement of the HLA-G molecule on SLE susceptibility and outcome.
系统性红斑狼疮（SLE）是一种影响多个器官和系统的炎症性自身免疫性疾病。尽管其病因可能是多因素的，但其确切病因仍不清楚。人类白细胞抗原G（HLA - G）是一种非经典的主要组织相容性复合体I类分子，其特点是表达受限和低DNA多态性。HLA - G通过不同机制发挥免疫抑制作用。在炎症性疾病中，有人推测HLA - G表达可能是组织保护免受炎症反应加剧的一种可能机制。在HLA - G基因的3'非翻译区（3'UTR），存在一个14 bp的插入/缺失多态性（rs1704），已证明其会影响mRNA稳定性。这种多态性对疾病易感性的影响存在争议。同样在3'UTR中，在+3142位置存在一个单核苷酸多态性C/G（rs1063320），该位置可能是微小RNA（miRNA）的结合位点，并对miRNA亲和力有影响。在本研究中，我们分析了195例欧洲裔女性SLE患者的+3142C>G和14 bp多态性。我们的研究结果显示，与对照组相比，患者中+3142G等位基因频率显著增加（0.58对0.47，P = 0.011）。此外，患者中GG基因型的频率更高（OR = 1.90，95%CI：1.08 - 3.42）。两种多态性的双杂合子患者的系统性红斑狼疮疾病活动指数（SLEDAI）平均值比仅一种变体的杂合子或非杂合个体更轻（分别为1.56对3.15和3.26，校正P = 0.044）。这些结果表明HLA - G分子与SLE易感性和疾病转归有关。
