Association of the HLA-G gene +3142C>G polymorphism with systemic lupus erythematosus

• Published in: Tissue antigens 2011-06, Vol.77 (6), p.540-545
• Main Authors: Consiglio, C. R., Veit, T. D., Monticielo, O. A., Mucenic, T., Xavier, R. M., Brenol, J. C. T., Chies, J. A. B.
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; Adult; Alleles; Autoimmune diseases; Binding Sites; Case-Control Studies; Etiology; Exons; Female; Gene deletion; Gene Frequency; Gene polymorphism; Genotype; Heterozygote; Heterozygotes; Histocompatibility antigen HLA; Histocompatibility Antigens Class I - genetics; HLA Antigens - genetics; HLA-G Antigens; human leukocyte antigen G; Humans; immunogenetics; Immunosuppression; Inflammation; Inflammatory diseases; Insertion; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Major histocompatibility complex; Male; MicroRNAs - metabolism; Middle Aged; miRNA; mRNA stability; polymorphism; Polymorphism, Genetic; Single-nucleotide polymorphism; Systemic lupus erythematosus
• ISSN: 0001-2815; 1399-0039
• DOI: 10.1111/j.1399-0039.2011.01635.x

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease that affects several organs and systems. Its etiology remains unknown, although it is probably multifactorial. The human leukocyte antigen G (HLA‐G) is a nonclassic major histocompatibility complex I molecule characterized by restricted expression and low DNA polymorphism. HLA‐G plays a role in immunosuppression through different mechanisms. In inflammatory diseases, it has been postulated that HLA‐G expression may be a possible mechanism of tissue protection against exacerbated inflammatory response. On the 3′ untranslated region (3′ UTR) of the HLA‐G gene, there is an insertion/deletion polymorphism of 14 bp (rs1704) that was shown to influence the mRNA stability. The influence of this polymorphism in disease susceptibility is controversial. Also in the 3′ UTR there is a single nucleotide polymorphism C/G (rs1063320) on the position +3142, at a possible binding site for microRNAs (miRNAs) and having an influence on miRNA affinity. In this study, we analyzed the +3142C>G and the 14 bp polymorphisms in 195 SLE European‐derived female patients. Our findings show a significant increase of the +3142G allele frequency among patients as compared with controls (0.58 vs 0.47, P = 0.011). Also, patients presented a higher frequency of the GG genotype (OR = 1.90, 95% CI: 1.08–3.42). Double heterozygotes for the two polymorphisms presented a milder mean systemic lupus erythematosus disease activity index (SLEDAI) than heterozygotes for only one of the variants or non‐heterozygous individuals (1.56 vs 3.15 and 3.26, respectively, corrected P = 0.044). These results suggest the involvement of the HLA‐G molecule on SLE susceptibility and outcome.