HLA-G and susceptibility to develop celiac disease

The Human Leukocyte Antigen-G has immunomodulatory function and its expression has been associated with several diseases. In our study we analyzed HLA-G polymorphisms in order to evaluate their possible association with susceptibility to celiac disease development. A total of 420 celiac patients and 509 controls were genotyped for HLA-G polymorphisms. We sequenced 800 bp upstream the ATG codon (5′ upstream regulatory region) and the whole 3′ untranslated region of the HLA-G gene, whereas the ΔC deletion at exon 3 was detected by RFLP-PCR. Five polymorphisms (namely −477 C>G, −369 C>A, 14 bp del/ins, 3187 A>G, 3196 C>G) and one haplotype (TCGGTACGAAITCCCGAG) were significantly more frequent in celiac patients than controls and associated with increased disease susceptibility. The 14 bp I/I, 3187 G/G, 3196 G/G genotypes and TCGGTACGAAITCCCGAG haplotype, were still significantly associated with increased disease susceptibility (and in addition also the 3003 C/C genotype) when the analysis was restricted to patients and controls presenting the DQ2.5 or DQ8 HLA-DQ celiac disease risk haplotypes. Our findings indicate an association between HLA-G gene polymorphisms and susceptibility to celiac disease development, suggesting that HLA-G molecule is possibly involved in the pathogenesis of the disease.