engleski

Association of the vitamin D receptor gene variants with Graves' disease in the Croats

Contradictory results regarding the relationship between common alleic variants and graves' disease (GD) in divergent populations have been reported, but few studies analysed the associations in terms of haplotypes. Three VDR gene polymorphisms in 151 GD patients of Eastern Croatian origin, and 139 ethnically and age-matched, unrelated, healthy controls, were assessed with a PCR amplification-restriction fragment (BsmI/ApaI/TaqI endonuclease) assays. All subjects gave informed, written consent. Case-control allelic and genotype frequencies were compared with Chi2-test with Yates' and Bonferroni's corrections. The VDR gene 5'-3' haplotype frequencies for unphased case-control genotype data, and estimated haplotype effect types (ß) with likelihood ratio (LR) statistics were inferred with an expectation-conditional maximization algorithm. All DNA data sets were in Hardy-Weinberg equilibrium. The allelic odds ratios (OR) with 95% confidence intervals were 0.63 (0.46-0.88, p=0.009), 0.6 (0.43-0.83, p=0.003), and 1.61 (1.14-2.25, p=0.008) for BsmI B, ApaI A and TaqI T alleles, respectively. The BsmI BB (OR=0.37 (0.2-0.69), p=0.002) and ApaI AA genotypes (OR=0.49 (0.28-0.84, p=0.014) were undertransmitted to the patients, whereas TaqI TT (OR=1.96 (1.21-3.15, p=0.008) and ApaI aa genotypes (OR=2.17 (1.21-3.89, p=0.013) were overrepresented in the patients. Based on the Akaike Information Criterion, and pairwise linkage disequilibrium patterns, an extended 5'-3' joint haplotype model analysis showed preferential association of baT (ß=0.77+/-0.28, LR=16.2, p=0.0003), aT (ß=0.7+/-0.26, LR=16.3, p=0.0003) and ba (ß=0.62+/-0.3, LR=17, p=0.0007) haplotypes with the GD phenotype under a dominant model, whereas Bt haplotype (ß=-1.1+/-0.43, LR=13.3, p=0.0013) showed putative protective effect under the assumption of recessive model. These data suggest an association of VDR gene 3'-variants with GD phenotype in this ethnic group. Further studies, that dissect the contribution of population-specific phenomena, are needed to clarify the mechanisms underlying the observed associations.

Graves disease; Croatia; Polymorphism; RestrictionFragment Length; Haplotypes; Genetic Predisposition to Disease; Receptors; Calcitriol

nije evidentirano