| Abstract | Cilj istraživanja: Povezanost dijabetesa tipa 1 i HLA sustava predmetom je istraživanja posljednjih četrdesetak godina. Cilj je ovoga istraživanja je analizirati raspodjelu alelnih (HLA-A, -B, -DRB1, -DQB1, -DQA1 lokusa) i haplotipnih (DRB1-DQA1-DQB1) varijanti gena HLA sustava te odrediti njihovu povezanost s T1DM-om, u smislu prisutnosti tih varijanti u oboljelih na području istočne Hrvatske.
Materijali i metode: Iz EDTA uzoraka pune krvi 81 pacijenta oboljeloga od T1DM-a izolirana je DNA i svi su tipizirani PCR-SSP metodom niske ili visoke rezolucije. Kao kontrole korišteni su ranije objavljeni rezultati HLA tipizacije zdravih, nesrodnih osoba.
Rezultati: Značajna razlika u učestalosti alela kod pacijenata i kontrolne skupine uočena je za alel HLA-B*8, međutim značajnost alela HLA razreda I pripisana je neravnoteži udruživanja s alelima HLA razreda II. Učestalost alela HLA razreda II u korist pacijenata je: DQB1*03:02 (31,86 %); DQB1*02 (32,10 %); DRB1*04 (31,48 %); DRB1*03 (27,16%); DQA1*03:01 (37,50 %). Niža učestalost alela kod pacijenata je: DQB1*06 (6,79 %); DRB*15 (1,85 %); DRB*11 (5,56 %); DQA1*01:02 (7,5 %). Najučestaliji haplotipovi među pacijentima su i prema literaturi navedeni kao pozitivno povezani s T1DM-om: DRB1*04-DQA1*03:01-DQB1*03 (DQ8) (37,%) i DRB1*03-DQA1*05:01-DQB1*02:01 (26,25 %) i samo 7/40 (17,5 %) pacijenata nema niti jedan od spomenutih haplotipova.
Zaključak: Rezultati istraživanja i na malom uzorku, kakav je naš, pokazuju da je genetska sklonost pacijenata oboljelih od T1DM-a s područja istočne Hrvatske povezana s alelima HLA DR i DQ lokusa, točnije s pojedinim haplotipnim kombinacijama (DQB1*03-DQA1*05:01-DQB1*02:01/DRB1*04-DQA1*03:01-DQB1*03 (DQ8)), što je u skladu s objavljenim rezultatima istraživanja na populacijama bijelaca. |
| Abstract (english) | The aim of the study: The link between type 1 diabetes (T1DM) and the HLA system has been continuously studied for the past 40 years. The aim of this study was to investigate the distribution of allelic- (HLA-A, -B, -DRB1, -DQB1, -DQA1 loci) and haplotype- (DRB1-DQA1-DQB1) variants of the HLA system genes and their possible connection to T1DM as risk variants in diabetic patients of Eastern Croatia.
Materials and Methods: DNA was isolated from whole blood EDTA samples of 81 patients diagnosed with T1DM. HLA typing was done using high or low resolution PCR-SSP method. The data for control samples wereobtained from previously typed, healthy, non-related individuals.
Results: Significant differences in allele frequencies between diabetic patients and the control group were found for HLA-B*08 and -B*07 allele. However, the significance of HLA class I alleles has been ascribed to the linkage disequilibrium with class II alleles. The frequencies of class II alleles in favor of patients were: DQB1*03(DQ8) (31.86%); DQB1*02 (32.10 %); DRB1*04 (31.48 %); DRB1*03 (27.16%); DQA1*03:01 (37.50 %). DQB1*06 (6.79 %); DRB*15 (1.85 %); DRB*11 (5.56 %); DQA1*01:02 (7.5 %) showed lower allele frequencies in patients. The most frequent haplotypes among patients were also in concordance with the existing literature as positively correlated to T1DM: DRB1*04-DQA1*03:01-DQB1*03 (DQ8) (37 %) and DRB1*03-DQA1*05:01-DQB1*02:01 (26.25 %). Only 7/40 (17.5 %) of patients had none of the abovementioned haplotypes.
Conclusion: The results of this study, even in a small sample pool as ours, indicate that the genetic susceptibility in T1DM patients of Eastern Croatia is linked to the alleles of the HLA DR and DQ locus, precisely to the following haplotype combinations: DQB1*03-DQA1*05:01-DQB1*02:01 / DRB1*04-DQA1*03:01-DQB1*03 (DQ8). The results are in agreement with the available research results of studies in Caucasians. |
