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

摘要

Objective To evaluate the possible association of the HLA-G 14 bp insertion (+14 bp) and de-letion (-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 sig-nificant 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 anti-bodies and patients with positive anti-histone antibodies when compared with the respective antibody-negative pa-tients .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 sus-ceptibility for the autoantibody production in rheumatic diseases .%目的 研究人类白细胞抗原(HLA)-G 14 bp插入(+14 bp)/缺失(-14 bp)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 14 bp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,HLA-G 14 bp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 14 bp插入/缺失多态性分布差异有统计学意义(P<0.05),抗snRN P抗体阳性组+14 bp等位基因频率[P=0.0015,OR=1.783,95%CI(1.245,2.553)]与+14 bp/-14 bp杂合子基因型频率[P=0.0001,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-14 bp等位基因频率[P=0.0001,OR=2.315,95%CI(1.563,3.429)]和-14 bp/-14 bp纯合基因型频率[P=0.0001,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.