Palafox-Sánchez Claudia Azucena, Oregon-Romero Edith, Salazar-Camarena Diana Celeste, Valle Yeminia Maribel, Machado-Contreras Jesús René, Cruz Alvaro, Orozco-López Mariana, Orozco-Barocio Gerardo, Vázquez-Del Mercado Mónica, Muñoz-Valle José Francisco
Instituto de Investigación en Ciencias Biomédicas (IICB), Departamento de Clínicas Médicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México.
Departamento de Inmunología y Reumatología del Hospital General de Occidente, Secretaria de Salud Jalisco, Zapopan, Jalisco, México.
Clin Exp Med. 2015 Nov;15(4):439-46. doi: 10.1007/s10238-014-0315-4. Epub 2014 Sep 25.
Systemic lupus erythematosus (SLE) is the prototype autoimmune rheumatic disease. The etiology of this disease is incompletely understood; however, environmental factors and genetic predisposition are involved. Cytokine-mediated immunity plays a crucial role in the pathogenesis of SLE. We investigate the association of interleukin-10 (IL-10) promoter polymorphisms and their haplotypes in SLE patients from the western Mexico. One hundred and twenty-five SLE patients fulfilling the 1997 ACR criteria and 260 unrelated healthy subjects (HS), both Mexican mestizos, were genotyped for IL-10 -1082A>G, -819C>T, and -592C>A polymorphisms. Haplotypes were inferred using the expectation-maximization algorithm, then allele and haplotype distributions were compared between patients and HS, as well as patients with different clinical variables. We identified at -1082, -819, and -592 four predominant haplotypes ACC (43.70 % in patients vs 46.55 % in HS), ATA (21.45 vs 22.97 %), GCC (16.28 vs 14.21 %), and GTA (14.12 vs 14.12 %). The ATC haplotype was more frequent in SLE respect to HS, suggesting a risk effect (3.23 vs 1.05 %; OR 3.55, CI 1.14-11.11; p = 0.0293). SLE patient carriers of -592 CC genotype as well as the dominant model of inheritance showed higher sIL-10 respect to AA genotype, suggesting that -592 C allele is associated with increased production of the cytokine (p < 0.05). The ACC haplotype had higher IL-10 serum levels and higher values of Mexican version of the Systemic Lupus Erythematosus Disease Activity Index compared with the other haplotype carriers; however, no association was found regarding autoantibodies. Our data suggest that the IL-10 promoter haplotypes play an important role in the risk of developing SLE and influence the production of IL-10 in Mexican population. Nevertheless, further studies are required to analyze the expression of mRNA as well as to investigate the interacting epigenetic factors that could help to define the true contribution of this marker in SLE pathogenesis.
系统性红斑狼疮（SLE）是自身免疫性风湿疾病的典型代表。该疾病的病因尚未完全明确；然而，环境因素和遗传易感性与之相关。细胞因子介导的免疫在SLE发病机制中起关键作用。我们研究了墨西哥西部SLE患者白细胞介素-10（IL-10）启动子多态性及其单倍型的关联。对125例符合1997年美国风湿病学会（ACR）标准的SLE患者和260例无关健康对照者（HS）进行基因分型，二者均为墨西哥混血，检测IL-10 -1082A>G、-819C>T和-592C>A多态性。使用期望最大化算法推断单倍型，然后比较患者与HS之间以及不同临床变量患者之间的等位基因和单倍型分布。我们在-1082、-819和-592位点鉴定出四种主要单倍型ACC（患者中占43.70%，HS中占46.55%）、ATA（21.45%对22.97%）、GCC（16.28%对14.21%）和GTA（14.12%对14.12%）。与HS相比，ATC单倍型在SLE中更常见，提示有风险效应（3.23%对1.05%；比值比3.55，95%置信区间1.14 - 11.11；p = 0.0293）。-592 CC基因型的SLE患者携带者以及显性遗传模型显示，相对于AA基因型，其可溶性IL-10水平更高，提示-592 C等位基因与细胞因子产生增加相关（p < 0.05）。与其他单倍型携带者相比，ACC单倍型的血清IL-10水平更高，且墨西哥版系统性红斑狼疮疾病活动指数值更高；然而，未发现与自身抗体有关联。我们的数据表明，IL-10启动子单倍型在SLE发病风险中起重要作用，并影响墨西哥人群中IL-10的产生。尽管如此，仍需要进一步研究来分析mRNA的表达，并研究可能有助于确定该标志物在SLE发病机制中真正作用的相互作用的表观遗传因素。
