engleski

Vitamin D Receptor Polymorphism and Susceptibility to Hashimoto's thyroiditis in the Croatian Female Population

Hashimoto's thyroiditis (HT) is an organ-specific T-cell mediated complex disease with a strong genetic component. Aim. To evaluate the effect of vitamin D3 receptor (VDR) gene BsmI/TaqI restriction fragment length polymorphisms on HT susceptibility in a subset of Caucasian female Croatian patients. Methodes. Plasma FT4, FT3, TSH and TPOAt-IgGs were determined by commercially available kits. VDR gene polymorphisms in 109 HT female patients, and 129 ethnically and age-matched, unrelated, healthy female controls, were assessed by BsmI/TaqI endonuclease digestion after PCR amplification with sequence-specific primers. Measurements with skewed distribution are presented as medians and interquartile ranges and were normalized by log10-transformation before statistical analysis. Single-locus case-control allelic and genotype frequencies were compared with Pearson's χ 2-test with Bonferroni's corrections or with Fisher exact test whenever appropriate. The strength of association was estimated by crude odds ratios (OR) with the respective 95% confidence intervals (95% CI). Global effects of genotypes on plasma TPOAt and TSH concentrations at the time of diagnosis were assessed using nonparametric Mann-Whitney and Kruskall-Wallis tests. Associations between each VDR RFLP and TPOAt plasma levels were investigated using classical generalized linear model assuming additive allele effects. Monte Carlo simulations were carried out to evaluate empirical p-values of the nonparametric, χ 2 and Fisher exact tests. Results. HT was defined by positive autoantibodies to TPO, characteristic echosonographic findings and histological confirmation of a lymphocytic infiltrate in a fine needle aspiration biopsy regardless of thyroid function. In 80 patients (73%), biochemical hypothyroidism was already present at the time of diagnosis. No evidence of age-specific effects on risk was found (p=0.971, Breslow-Day test). All DNA datasets in both groups were in Hardy-Weinberg equilibrium. The BsmI B variant appears to function under a recessive model, where homozygous women for the major allele were underrepresented in the patient group (16.5% vs. 30.2%, patients vs. controls, exact p=0.015, OR=0.46, 95% CI=0.24-0.85). Analysis of the TaqI polymorphism revealed no significant difference between HT patients and controls. After adjustment for plasma logTSH concentrations, BsmI locus seemed to contribute to plasma logTPOAt variability at the time of diagnosis (p=0.035, GLM, R2a=0.057), with significantly higher logTPOAt titers in BB homozygotes. Conclusion. Presented data suggest weak protective effect against HT phenotype in BsmI BB carriers. Conversely, TaqI alleles do not contribute substantially to HT susceptibility in the population analyzed. There is no clear-cut relationship between thyroid hormonal status, age at diagnosis and any VDR gene polymorphism in different genetic models.

Croatia; women; genotype; Hashimoto's thyroiditis; polymorphism; susceptibility; vitamin D; receptor

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