HLA-G 14 bp D/I polymorphism linked to celiac disease
MedWire News: Study findings suggest nonclassical major histocompatibility class I HLA-G gene variants increase the risk for celiac disease.
Ludovica Segat (IRCCS Burlo Garofolo, Trieste, Italy) and colleagues found that individuals who carry both HLA-DQ2 and HLA-G I alleles have an increased risk for celiac disease compared with those carrying the DQ2 but not the I allele.
Research has shown that the HLA-G 14 bp deletion/insertion (D/I) polymorphism has a functional effect on mRNA stability but, until now, no association studies concerning HLA-G polymorphisms and celiac disease have been conducted.
For the study, the HLA-G 14 bp D/I polymorphism (rs1704) was detected by polymerase chain reaction in 522 Italian Caucasian celiac disease patients, aged on average 18.7 years, and 400 healthy Italian control individuals.
The presence of DQ2 or HLA DQ8 was associated with a respective 7.31- and 2.50-fold increased risk for celiac disease. In addition, the 14 bp D/I allele occurred significantly more often in celiac disease patients than in healthy controls, at 49% versus 42%, conferring a 1.35-fold increased risk for the disease.
The team also found that the homozygous I/I genotype occurred significantly more frequently in celiac disease patients than in healthy controls, at 25% versus 15%, respectively. Further analyses showed that the predisposing effect of the I allele was exerted only in homozygous carriers.
When the researchers stratified celiac disease patients for the presence of HLA-DQ2, they found significant differences in the frequencies of both the 14 bp D/I alleles and genotypes between DQ2-positive patients and healthy controls, but not between non-DQ2 patients and controls. Indeed, the presence of the I allele was associated with a 1.56-fold increased risk for celiac disease in DQ2-positive patients.
"These results suggest that the effect of HLA-G polymorphism is restricted for HLA-DQ2 and not due to a possible linkage disequilibrium between the I allele and HLA class II alleles," comment Segat and co-authors.
Lastly, the investigators found that patients who had both the I allele and DQ2 had a 9.36-fold increased risk for celiac disease, which was higher than the risk conferred by HLA-DQ2 regardless of the D/I allele (odds ratio [OR]=7.31) or by the risk conferred by DQ2 in the absence of the I allele (OR=5.98).
"HLA-G could be hypothesized as a new modifier gene associated with celiac disease," write Segat et al in the American Journal of Gastroenterology.
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By Ingrid Grasmo