engleski

VDR Gene AssociationN with Graves' Disease and Hashimoto’ s Thyroiditis in Eastern Croatia Population

Grave's disease (GD) and Hashimoto's thyroiditis (HT) are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Abundant experimental data have pointed to a strong genetic influence of VDR gene on immunomodulatory, suppressive and regulatory effects of the immune system, suggesting VDR gene as potential functional candidate gene in the pathogenesis of autoimmune processes. The differential diagnosis of two distinct autoimmune thyroid disorders (AITD) in patients with diffuse goiter and positive serum TPO antibodies was primarily based on biochemical results concerning serum TSH, TSH-R autoantibodies, FT4 and FT3 levels. GD patients (n=146), HT patients (n=130) and ethnically matched, (TPOAt-negative) euthyroid controls (n=133) with no clinical evidence or family history of thyroid or autoimmune diseases were genotyped for VDR gene polymorphisms by BsmI and TaqI endonuclease digestion after PCR amplification with sequence-specific primers. Data were analyzed by χ 2-test, information analysis, multivariate, haplotypic log-regression and adjusted odds ratios (OR) with 95% confidence intervals (95% CI) were calculated. Following results were obtained: in age-adjusted, codominant analysis for AITD phenotype, BsmI “ bb” genotype (38.4% vs 28.6%, patients vs controls, OR=3.09, 95% CI [1.69-5.63] by comparison to the reference “ BB” genotype, P=0.0002), was significantly overrepresented in patients. Also, in age/gender-adjusted, allele analysis, “ b” allele (62.9% vs 49.6%, patients vs controls, OR=1.70, 95%CI [1.27-2.29], P=0.00042) was significantly more prevalent in the patients group. Haplotype combination, which conferred the strongest association with AITD phenotype, was “ bT” haplotype (OR= 1.61, 95% CI [1.15-2.27], P=0.0059). No significant difference in the frequencies of the TaqI genotypes was observed between AITD and control groups in either model studied. These findings suggest that VDR gene BsmI polymorphism is associated with susceptibility to AITD in a subset of patients from Eastern Croatia.

DR gene polymorphisms; Graves' disease; Hashimoto's thyroiditis; eastern Croatia

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