HLA Haplotype Association with Celiac Disease in Albanian Pediatric Patients from Kosovo

Abstract

Genetic predisposition to celiac disease (CD) is strongly associated with the presence of HLA alleles in the individual genotype encoding HLA-DQ2 and/or HLA-DQ8 heterodimers. The main aim of this study was to analyze the HLA-A, -B, -DRB1, and -DQ allele and five-locus haplotype frequencies in 60 Albanian pediatric CD patients and 124 non-CD children from Kosovo. The most prevalent haplotype in patients was the ancestral AH 8.1 haplotype present in 22.5% of the cases compared to 2.8% of the controls (P<0.0001). Additionally, two other haplotypes were also overrepresented in patients (HLA-A∗02~B∗50~DRB1∗07~DQA1∗02:01~DQB1∗02:02 and HLA-A∗68~B∗44~DRB1∗07~DQA1∗02:01~DQB1∗02:02). Analysis showed that 95.0% of CD patients and 43.3% of controls were carriers of HLA-DQ2 and/or HLA-DQ8 heterodimers. The most frequent CD-predisposing HLA-DQ haplotypes in patients were HLA-DQ2.5 (46.7%) and HLA-DQ2.2 (11.6%), while the most prevalent genotypes were HLA-DQ2.5/DQX (58.3%) and HLA-DQ2.5/DQ2.2 (20.0%). The frequency of the HLA-DQ8 heterodimer among CD patients (4.2%) compared to the control group (8.1%) was without statistical significance. The given data demonstrate differences in the distribution of HLA haplotypes among Albanian CD patients from Kosovo in comparison to other European and non-European populations, as well as provide additional population data to supplement the thus far undisputed importance of the role of HLA-DQ2 and HLA-DQ8 heterodimers in the development of CD.