HLA-G 14 bp deletion/insertion polymorphism in celiac disease

Area of Science:

• Immunogenetics
• Gastroenterology

Background:

• The human leukocyte antigen-G (HLA-G) is a nonclassical MHC class I molecule with immunomodulatory and tolerogenic functions.
• Its role in autoimmune diseases like celiac disease (CD) is under investigation due to its potential to influence immune responses.

Purpose of the Study:

• To investigate the association between the HLA-G 14 bp deletion/insertion (D/I) polymorphism and the risk of developing celiac disease (CD).
• To evaluate the effect of this polymorphism, particularly in relation to the known CD risk factor, HLA-DQ2.

Main Methods:

• Genotyping of the HLA-G 14 bp D/I polymorphism (rs1704) using polymerase chain reaction (PCR).
• Confirmation of polymorphism by direct sequencing.
• Analysis in 522 CD patients and 400 healthy controls, stratified by HLA-DQ2 status.

Main Results:

• The 14 bp insertion (I) allele and the I/I homozygous genotype were significantly more prevalent in CD patients compared to healthy individuals.
• The I allele was associated with an increased risk of CD (Odds Ratio 1.35), consistent with a recessive genetic model (P<0.001).

Conclusions:

• The HLA-G D/I polymorphism influences CD risk, independent of linkage disequilibrium with HLA-DQ2.
• Carrying the HLA-G I allele increases CD risk, and this risk is further elevated in individuals who also possess the HLA-DQ2 genotype.