Summary:
In this study we aimed at assessing the HLA-DRB1, DQA1 και DQB1 allelic,
haplotypic and genotypic distribution in a large cohort of children with celiac
disease (CD) in Greece, compared with the general population and the evaluation
of the HLA effect on disease susceptibility. Moreover, this study evaluated
correlations between the HLA-related genetic background of CD with clinical,
epidemiological, serological and histological characteristics. A total of 118
children of Greek origin with CD, as well as a panel of 120 healthy individuals
of the same origin served as controls and were included in the analysis. The
symptomatic children were divided into 3 groups according to the number of
DQB1*02 alleles: group A, homozygous; group B, heterozygous; group C, negative.
HLA genotyping was performed by PCR-SSO and PCR-SSP methods. Higher frequencies
for HLA-DQB1*02:01, DQB1*02:02, DQA1*02:01, DQA1*05:01, DRB1*03 and DRB1*07
were observed in CD patients compared to controls. In contrast, frequencies of
HLA-DQB1*03:01, DQB1*05:01, DQB1*05:02, DQA1*01:01, DQA1*01:02, DQA1*01:04,
DQA1*05:05, DRB1*01 and DRB1*16 were significantly lower in patients. The
haplotype mainly associated with CD was DR3-DQ2, followed by DR7-DQ2. Only one
in 118 patients was DQ2/DQ8/DQA1*05/DQB1*02-negative and this corresponds to a
1/118=0.8% probability of combined DQ2/DQ8/α5/β2 negativity in CD patients. A
statistically significant correlation was recorded between EMA titer and the
number of DQB1*02 alleles: HLA-DQB1*02 homozygotes had significantly higher EMA
titers compared to HLA-DQB1*02 negative patients. The present study shows for
the first time in the Greek pediatric population the frequency of HLA class II
alleles, haplotypes and genotypes, and confirms the evidence supporting a
strong genetic predisposition for CD associated with the HLA class II alleles
DQB1*02-DQA1*05 encoding the serological specificity DQ2.
Keywords:
Celiac disease, HLA class II genes, HLA-DQ2, HLA-DQ8, Haplotypes
