AB0009 Association of an HLA-G 3’UTR haplotype with susceptibility to rheumatoid arthritis: A north-south analysis in two independent brazilian cohorts

Background HLA-G may exert long-term immunotolerogenic effects through the generation of suppressor cells [reviewed in [1]]. Such features render HLA-G an attractive candidate gene for susceptibility to immune mediated diseases. Indeed, our group has observed a positive association of a 3’UTR haplotype encompassing the 14bp locus and the +3142C/G (rs1063320) and disease susceptibility in patients with systemic lupus erythematosus [2]. Objectives To investigate the genetic influence of the two HLA-G 3’UTR polymorphisms – the 14 bp insertion/deletion (rs1704) and the +3142C>G (rs1063320) – in the susceptibility to rheumatoid arthritis in a double-center study comprising a Southern-Brazilian cohort from Porto Alegre and Northern-Brazilian cohort from the city of Belém. Methods A total number of 546 RA patients and 531 controls was PCR genotyped for the two polymorphisms. Results Haplotype frequencies differed significantly between control groups from the Northern and Southern cohorts. After adjusting for city of origin and gender, we observed that female patients presented a higher frequency of the deletion-G (D/G) haplotype (OR=1.634, 95% CI=1.128–2.368, P=0.009). After stratifying for RF positivity, only the female RF+ group of patients presented statistical significance (OR=1.829, 95%C.I =1.243–2.690, P=0.002) - Table 1. Table 1. HLA-G D/G carrier frequencies in patients and comparison with controls AllFemalesMales N/Total (freq)N/Total (freq)N/Total (freq) Porto Alegre (South) Controls0.206 (59/287)0.133 (16/120)a,b0.257 (43/167) Patients (all)0.235 (80/340)0.242 (67/277)a0.206 (13/63) RF+0.238 (67/281)0.247 (56/227)b0.204 (11/54) RF–0.232 (13/56)0.234 (11/47)0.222 (2/9) Belém (North) Controls0.338 (75/222)0.302 (38/126)c0.385 (37/96) Patients (all)0.360 (71/197)0.374 (68/182)0.200 (3/15) RF+0.405 (60/148)0.414 (58/140)c0.250 (2/8) RF–0.242 (8/33)0.286 (8/28)0.0 (0/5) aP=0.015, bP=0.017, cP=0.072. Conclusions Our results suggest a differential influence of HLA-G 3’UTR polymorphisms in disease susceptibility, with the D/G haplotype as a risk factor for RA in RF+ females. References Carosella ED, HoWangYin K-Y, Favier B, LeMaoult J. Hla-g-dependent suppressor cells: Diverse by nature, function, and significance. Human immunology 2008;69:700-7. Consiglio CR, Veit TD, Monticielo OA, et al. Association of the hla-g gene +3142c>g polymorphism with systemic lupus erythematosus. Tissue Antigens 2011;77:540-5. Disclosure of Interest None Declared