HLA-G 3' untranslated region haplotypes and celiac disease in Morocco

Celiac disease (CD) is a multifactorial autoimmune enteropathy due to gluten intolerance in genetically predisposed individuals, with the interaction of environmental factors. In addition to the well-known HLA-DR/DQ associations involved in CD (DQ2.5, DQ2.2 and DQ8 haplotypes), some other genes have been investigated and associated with disease susceptibility and clinical forms. HLA-G is a nonclassical HLA and an immune checkpoint molecule. HLA-G expression and polymorphisms, mainly in the 30 untranslated regulatory region (UTR), is under examination in several infectious, inflammatory and autoimmune diseases, including CD. Here we report the HLA-G 30 UTR polymorphisms (HLA-G14bpins/del, +3003 T/C, +3010C/G, +3027C/A, +3035C/T, +3142C/G, +3187A/G, +3196C/G and +3227G/A) and 30 UTR haplotypes in patients with CD from Morocco, assessed using direct sequencing. The allele and genotype frequencies were calculated and the 30 UTR haplotypes were estimated with the expectation-maximization method; associations between genotype and haplotype frequencies (hf) and CD were analyzed. Results showed no statistically significant differences in HLA-G 30 UTR allele and genotype frequencies between CD and the control population (Metalsa from Morocco). However, a significant association for some genotypes with the clinical presentation of CD was found in patients (p <= 0.02). The HLA-G 30 UTR haplotype distribution in patients and controls demonstrated an increased frequency of UTR-5 in CD (hf = 0.145, O.R. = 1.93, 95% CI: 1.01-3.67, p = 0.043). UTR-5 is considered to be associated with low HLA-G expression and has been hypothesized as a risk haplotype in some clinical conditions or based on environmental factors. These results suggest a possible additional genetic contribution of HLA-G to CD susceptibility in this geographic area.