HLA-G has well recognized tolerogenic properties in physiological and nonphysiological conditions. The 3′ untranslated region (3′UTR) of the HLA-G gene has at least 3 polymorphic sites (14-bpINS/DEL, +3142C/G, and +3196C/G) described as associated with posttranscriptional influence on messenger RNA production; however, only the 14-bpINS/DEL and +3142C/G sites have been studied in systemic lupus erythematosus (SLE).

We investigated the HLA-G 3′UTR polymorphic sites (14-bpINS/DEL, +3003C/T, +3010C/G, +3027A/C, +3035C/T, +3142C/G, +3187A/G, and +3196C/G) in 190 Brazilian patients with SLE and 282 healthy individuals in allele, genotype, and haplotype analyses. A multiple logistic regression model was used to assess the association of the disease features with the HLA-G 3′UTR haplotypes.

Increased frequencies were observed of the 14-bpINS (p = 0.053), +3010C (p = 0.008), +3142G (p = 0.006), and +3187A (p = 0.013) alleles, and increased frequencies of the 14-bpINS-INS (p = 0.094), +3010 C-C (p = 0.033), +3142 G-G (p = 0.021), and +3187 A-A (p = 0.035) genotypes. After Bonferroni correction, only the +3142G (p = 0.05) and +3010C (p = 0.06) alleles were overrepresented in SLE patients. The UTR-1 haplotype (14-bpDEL/+3003T/+3010G/+3027C/+3035C/+3142C/+3187G/+3196C) was underrepresented in SLE (p_corr = 0.035).

These results indicate that HLA-G 3′UTR polymorphic sites, particularly +3142G and +3010C alleles, were associated with SLE susceptibility, whereas UTR-1 was associated with protection against development of SLE.