HLA-G and susceptibility to develop celiac disease

Hum Immunol. 2015 Jan;76(1):36-41. doi: 10.1016/j.humimm.2014.12.006. Epub 2014 Dec 11.

Abstract

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 800bp 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, 14bp 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 14bp 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.

Keywords: Celiac disease; Human Leukocyte Antigen (HLA)-G; Inflammation; mRNA stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Case-Control Studies
  • Celiac Disease / genetics*
  • Celiac Disease / immunology
  • Celiac Disease / pathology
  • Child
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • HLA-DQ Antigens / genetics
  • HLA-DQ Antigens / immunology
  • HLA-G Antigens / genetics*
  • HLA-G Antigens / immunology
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Retrospective Studies

Substances

  • HLA-DQ Antigens
  • HLA-G Antigens