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

Celiac disease (CD) is a multifactorial autoimmune enteropathydue to gluten intolerance in genetically predisposedindividuals, with the interaction of environmental factors.In addition to the well-known HLA-DR/DQ associationsinvolved in CD (DQ2.5, DQ2.2 and DQ8 haplotypes), someother genes have been investigated and associated withdisease susceptibility and clinical forms. HLA-G is a nonclassicalHLA and an immune checkpoint molecule.HLA-G expression and polymorphisms, mainly in the 30untranslated regulatory region (UTR), is under examinationin several infectious, inflammatory and autoimmunediseases, including CD. Here we report the HLA-G 30UTR 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 inpatients with CD from Morocco, assessed using directsequencing. The allele and genotype frequencies were calculatedand the 30 UTR haplotypes were estimated withthe expectation-maximization method; associationsbetween genotype and haplotype frequencies (hf) and CDwere analyzed. Results showed no statistically significantdifferences in HLA-G 30 UTR allele and genotype frequenciesbetween CD and the control population (Metalsa fromMorocco). However, a significant association for somegenotypes with the clinical presentation of CD was foundin patients (p <= 0.02). The HLA-G 30 UTR haplotype distributionin patients and controls demonstrated an increasedfrequency 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 associatedwith low HLA-G expression and has been hypothesizedas a risk haplotype in some clinical conditions orbased on environmental factors. These results suggest apossible additional genetic contribution of HLA-G to CDsusceptibility in this geographic area.