人类白细胞抗原G 14pb插入/缺失多态性和风湿性疾病自身抗体产生的相关性研究

Association of HLA-G 14 bp insertion/deletion polymorphism with autoantibody production in patients with rheumatic diseases

目的研究人类白细胞抗原(HLA)-G 14bp插入(+14bp)/缺失(-14bp)多态性与风湿性疾病自身抗体生成的相关性。方法通过聚合酶链式反应(PCR)检测符合条件的292例风湿性疾病患者及257名健康体检者的HLA-G 14bp插入/缺失多态性的基因型分布。结果风湿性疾病患者和健康体检者相比,HLAG 14bp插入/缺失等位基因和基因型频率分布差异无统计学意义(P>0.05);抗核小RNA蛋白(snRNP)抗体、抗组蛋白抗体阳性患者与抗snRNP抗体、抗组蛋白抗体阴性者比较,HLA-G 14bp插入/缺失多态性分布差异有统计学意义(P<0.05),抗snRNP抗体阳性组+14bp等位基因频率[P=0.001 5,OR=1.783,95%CI(1.245,2.553)]与+14bp/-14bp杂合子基因型频率[P=0.000 1,OR=2.311,95%CI(1.393,3.834)]均增加,差异有统计学意义。抗组蛋白抗体阳性组-14bp等位基因频率[P=0.000 1,OR=2.315,95%CI(1.563,3.429)]和-14bp/-14bp纯合基因型频率[P=0.000 1,OR=2.884,95%CI(1.729,4.812)]增加,差异有统计学意义。结论 HLA-G 14bp插入/缺失多态性与自身抗体的产生存在相关性,可能是影响风湿性疾病自身抗体产生的易感遗传因素。

Objective To evaluate the possible association of the HLA-G 14 bp insertion（＋14 bp）and deletion（-14 bp）polymorphism with autoantibody production in patients with autoimmune rheumatic diseases.Methods A total of 292 patients with rheumatic diseases and 257 unrelated healthy controls from a Chinese Han population were HLA-G genotyped for the 14 bp insertion/deletion polymorphism.Results No statistically significant differences were observed in the frequencies of the HLA-G 14 bp insertion/deletion alleles or genotypes between controls and patients with rheumatic disease.However,significant differences in the distribution of the HLA-G 14 bp insertion/deletion polymorphism could be demonstrated for patients with positive anti-snRNP antibodies and patients with positive anti-histone antibodies when compared with the respective antibody-negative patients.The anti-snRNP antibodies positive group showed markedly increased frequencies of the＋14 bp allele[P〈0.01,OR=1.783,95%CI（1.245,2.553）]as well as the＋14 bp/-14 bp heterozygote[P〈0.01,OR=2.311,95%CI=（1.393,3.834）].Moreover,an increased frequencies of the-14 bp allele [P=0.0001,OR=2.315,95%CI=1.563,3.429]and the-14 bp/-14 bp homozygous genotype [P〈0.01,OR=2.884,95%CI（1.729,4.812）]were observed in the patients with positive anti-histone antibodies.Conclusion These findings are the first time to indicate that the HLA-G 14 bp insertion/deletion polymorphism could be a genetic risk factor influencing the susceptibility for the autoantibody production in rheumatic diseases.