Researchers Look at Influence of HLA Genes on Pediatric Celiac Disease

Celiac.com 07/29/2019 - Gluten and related prolamines trigger celiac disease in people who are genetically susceptible. The role of HLA-DQ genotypes is not well understood. A team of researchers recently set out to investigate the influence of HLA-DQ genotypes in clinical, serological and histological features related to celiac disease.

The research team included Eva Martínez-Ojinaga, Marta Fernández-Prieto, Manuel Molina, Isabel Polanco, Elena Urcelay and Concepción Núñez. They are variously affiliated with the Servicio de Gastroenterología y Nutrición Pediátrica, Hospital Universitario La Paz in Madrid, Spain; and the Laboratorio de investigación en Genética de enfermedades complejas, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC) in Madrid, Spain. 

Celiac.com Sponsor (A12):
The researchers conducted a retrospective observational study that included 463 Spanish patients with biopsy-proven celiac disease. The team collected clinical, serological, histological and HLA-DQ genetic data from each patient. They considered each patient's family history of celiac disease. 

They analyzed the data using chi-square tests or the Fisher’s exact test, along with multivariate logistic regression (after adjusting for age and sex) to assess the association between clinical and laboratory parameters with HLA-DQ.

The team's sample group was 62% females, with 86% showing classical clinical celiac presentation, and 99% showing positive anti-transglutaminase 2/endomysium antibodies. Patients averaged about 30 months old at disease onset. 

This study puts the rate of celiac disease in first-degree relatives at about five percent of total patients, while HLA-DQ genetics showed increased homozygosity of HLA-DQ2.5 and HLA-DQ8. 

In the non-celiac disease family history group, an association between delayed disease onset and HLA-DQ8 carriage was observed (p < 0.001), besides an influence of HLA-DQB1*02 gene dosage on clinical presentation and severity of histological damage (after adjusting for age and sex, p = 0.05 and p = 0.02, respectively) and a trend towards presence of specific antibodies (p = 0.09). Due to the small sample size, these associations could not be properly assessed in the group of patients with affected first-degree relatives.

For people with celiac disease, HLA-DQ genotypic frequency varies depending on the close family history of the disease. For people who do not have first-degree relatives with celiac disease, carrying the HLA-DQ2.5 gene with double dose of HLA-DQB1*02 seems correspond to classical clinical celiac presentation and more severe gut damage.

Clearly more study is needed to get a better picture of the connections between HLA-DQ genotypes and particular manifestations of celiac disease. However, this study offers one more piece of the celiac disease and genetics puzzle. Stay tuned as more information becomes available.

Read more in BMC Gastroenterology 201919:91