Sánchez E, Torres B, Vilches J R, López-Nevot M A, Ortego-Centeno N, Jiménez-Alonso J, González-Gay M A, de Ramón E, Sánchez-Román J, Núñez-Roldán A, Martín J, González-Escribano M F
Instituto de Biomedicina, CSIC, Hospital Virgen de las Nieves, Granada, Spain.
Rheumatology (Oxford). 2006 Sep;45(9):1096-100. doi: 10.1093/rheumatology/kel058. Epub 2006 Mar 14.
To replicate the described association between MHC class I chain-related A (MICA) gene polymorphism and susceptibility to systemic lupus erythematosus (SLE).
MICA transmembrane microsatellite polymorphism was genotyped using a polymerase chain reaction (PCR)-based method. Genotyping of HLA-B* and DRB1* was performed using PCR and detection with a reverse sequence-specific oligonucleotide (SSO) probe system. Combined data for these three loci (HLA-B*, DRB1* and MICA) were obtained from a total of 333 patients and 361 healthy controls.
Significant association with B08 [P < 10(-7), odds ratio (OR) 3.17, 95% confidence interval (CI) 2.02-5.00], DRB10301 (P < 10(-7), OR 2.07, 95% CI 1.59-2.68) and MICA5.1 (P = 0.01, OR 1.23, 95% CI 1.04-1.46) was observed. The combinations DRB10301-MICA5.1-B8 and HLA-DRB10301-B08-positive and MICA5-1-negative were more frequent among SLE patients (11.4 vs 3.3% in healthy controls, P = 3.9 x 10(-5), OR 3.76, 95% CI 1.85-7.73, and 6.9 vs 1.7%, P = 0.0007, OR 4.32, 95% CI 1.68-13.10, respectively). Additionally, individuals who were HLA-DRB10301-B08-negative and MICA5-1-positive were less frequent among patients (22.2 vs 31.3% in healthy controls, P = 0.007, OR 0.63, 95% CI 0.44-0.89) and the magnitude of the OR was similar to that obtained in individuals negative for all the three factors (OR 0.69, 95% CI 050-0.94). Further analysis performed to detect independent association strongly suggested that the association between MICA5.1 and SLE is secondary to the linkage disequilibrium of this allele with B08.
Our results do not support an independent association of MICA gene polymorphism with susceptibility to SLE.
重复已报道的MHC I类链相关A（MICA）基因多态性与系统性红斑狼疮（SLE）易感性之间的关联。
采用基于聚合酶链反应（PCR）的方法对MICA跨膜微卫星多态性进行基因分型。使用PCR和反向序列特异性寡核苷酸（SSO）探针系统检测对HLA - B和DRB1进行基因分型。这三个基因座（HLA - B*、DRB1*和MICA）的合并数据来自总共333例患者和361名健康对照。
观察到与B08 [P < 10(-7)，比值比（OR）3.17，95%置信区间（CI）2.02 - 5.00]、DRB10301（P < 10(-7)，OR 2.07，95% CI 1.59 - 2.68）和MICA5.1（P = 0.01，OR 1.23，95% CI 1.04 - 1.46）有显著关联。DRB10301 - MICA5.1 - B8组合以及HLA - DRB10301 - B08阳性且MICA5 - 1阴性在SLE患者中更常见（健康对照中为3.3%，SLE患者中为11.4%，P = 3.9 x 10(-5)，OR 3.76，95% CI 1.85 - 7.73；健康对照中为1.7%，SLE患者中为6.9%，P = 0.0007，OR 4.32，95% CI 1.68 - 13.10）。此外，HLA - DRB10301 - B08阴性且MICA5 - 1阳性的个体在患者中较少见（健康对照中为31.3%，患者中为22.2%，P = 0.007，OR 0.63，95% CI 0.44 - 0.89），且OR值大小与在所有三个因素均为阴性的个体中获得的值相似（OR 0.69，95% CI 0.50 - 0.94）。为检测独立关联而进行的进一步分析强烈表明，MICA5.1与SLE之间的关联是该等位基因与B08连锁不平衡的结果。
我们的结果不支持MICA基因多态性与SLE易感性的独立关联。
