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

HLA-G is a non-classical HLA-class Ib molecule and has multiple immunoregulatory properties. A 14bp insertion/deletion polymorphism in the HLA-G gene has been suggested to influence the expression of HLA-G and then to associate with certain pathological conditions, including autoimmune diseases. The aim of study was to evaluate the possible association of the HLA-G 14bp insertion (+14bp) and deletion (-14bp) polymorphism with autoantibody production in patients with autoimmune rheumatic diseases. A total of 504 patients with rheumatic diseases and 367 unrelated healthy controls from a Chinese Han population were HLA-G genotyped for the 14bp insertion/deletion polymorphism. No statistically significant differences were observed in the frequencies of the HLA-G 14bp insertion/deletion alleles or genotypes between controls and patients with rheumatic disease. However, significant differences in the distribution of the HLA-G 14bp 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 +14bp allele (P = 0.0001, OR = 1.794, 95% CI = 1.329 - 2.422) as well as the +14/-14bp heterozygotes (P = 0.0001, OR = 2.306, 95% CI = 1.511 - 3.521). Moreover, an increased frequencies of the -14bp allele (P = 0.0001, OR = 2.302, 95% CI = 1.657 - 3.198) and the -14/-14bp homozygous genotype (P = 0.0001, OR = 3.035, 95% CI = 1.974 - 4.667) was observed in the patients with positive anti-histone antibodies. These findings are the first time to indicate that the HLA-G 14bp insertion/deletion polymorphism could be a genetic risk factor influencing the susceptibility for the autoantibody production in rheumatic diseases.