Granados Julio, Zúñiga Joaquín, Acuña-Alonzo Víctor, Rosetti Florencia, Vargas-Alarcón Gilberto
Departamento de Inmunología y Reumatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México DF.
Gac Med Mex. 2006 May-Jun;142(3):195-9.
HLA alelles with susceptibility to systemic lupus erythematosus (SLE) have been found in many ethnic groups. In addition, some neighboring genes such as TNF-alpha and HSP70, that may contribute to this disease have also been described. Interestingly some of the genetic associations differ among several ethnic groups, which might suggest that ethnicity plays an important role in the predisposition to SLE. In this study, we analyze gene frequencies of HLA-DRB1, DQA1, DQB1, HSP70-2 alelles and the polymorphism of TNF-alpha promoter region among 81 Mexican mestizo SLE patients. A control group of 99 healthy Mexican mestizos was included. We found that the HLA-DRB10301-DQA10501-DQB10201 haplotype was significantly increased in SLE patients compared to healthy controls (p=0.01, OR=2.97, IC 95%=1.18-7.68). The DRB11501 allele was more frequent among patients than among controls. A significantly decreased frequency of the HLA-DRB1*0802 alelle in SLE patients was also observed. Since the HLA alelles associated with SLE are uncommon in Mexican ethnic groups, we performed admixture estimates analysis and found that the incorporation of SLE susceptibility markers in Mexican mestizo groups might have come from genetic admixture with Caucasian populations.
在许多种族群体中都发现了与系统性红斑狼疮(SLE)易感性相关的人类白细胞抗原(HLA)等位基因。此外,一些可能与该疾病有关的邻近基因,如肿瘤坏死因子-α(TNF-α)和热休克蛋白70(HSP70)也已被描述。有趣的是,一些基因关联在几个种族群体中存在差异,这可能表明种族在SLE的易感性中起着重要作用。在本研究中,我们分析了81例墨西哥混血SLE患者中HLA-DRB1、DQA1、DQB1、HSP70-2等位基因的基因频率以及TNF-α启动子区域的多态性。纳入了99名健康墨西哥混血个体作为对照组。我们发现,与健康对照组相比,SLE患者中HLA-DRB10301-DQA10501-DQB10201单倍型显著增加(p = 0.01,比值比[OR]=2.97,95%置信区间[IC]=1.18 - 7.68)。DRB11501等位基因在患者中的频率高于对照组。在SLE患者中还观察到HLA-DRB1*0802等位基因频率显著降低。由于与SLE相关的HLA等位基因在墨西哥种族群体中并不常见,我们进行了混合估计分析,发现墨西哥混血群体中SLE易感性标志物的纳入可能来自与白种人群体的基因混合。