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  • Title: Association of vitamin D receptor gene polymorphism with susceptibility to Graves' disease in Eastern Croatian population: case-control study.
    Author: Stefanić M, Karner I, Glavas-Obrovac L, Papić S, Vrdoljak D, Levak G, Krstonosić B.
    Journal: Croat Med J; 2005 Aug; 46(4):639-46. PubMed ID: 16100768.
    Abstract:
    AIM: To evaluate the effect of vitamin D3 receptor (VDR) gene BsmI/ApaI/TaqI restriction fragment length polymorphisms on Graves' disease susceptibility in a subset of patients from Eastern Croatia. METHODS: Graves' disease patients (n=110) and ethnically matched euthyroid controls (n=99) with no clinical evidence or family history of thyroid or autoimmune diseases were genotyped for VDR gene polymorphisms by BsmI/ApaI/TaqI endonuclease digestion after polymerase chain reaction amplification with sequence-specific primers. Data were analyzed by chi-square-test, and crude odds ratios (OR) with 95% confidence interval (95% CI) were calculated. RESULTS: The ApaI "AA" (14.5% vs 30.3%, patients vs controls, respectively, OR=0.39, 95% CI [0.2-0.77], P=0.01) and BsmI "BB" (7.3% vs 23.2%, OR=0.26 [0.11-0.61], P=0.002) genotypes were significantly underrepresented in patients, whereas ApaI "aa" (28.2% vs 9.1%, OR=3.92 [1.76-8.74], P=0.001) and TaqI "TT" (51.8% vs 31.3%, OR=2.36 [1.34-4.16], P=0.004) genotypes were significantly more frequent in patients than controls. The genotype combination, which conferred the strongest protection against Graves' disease, was "BBAAtt" (2.7% vs 17.2%, OR=0.14 [0.04-0.48], P=0.001). CONCLUSION: These findings suggest that VDR gene BsmI/ApaI/TaqI polymorphisms are associated with Graves' disease susceptibility in a subset of patients from Eastern Croatia. The ApaI and BsmI "AA" and "BB" genotypes, respectively, as well as combined "BBAAtt" genotype, appeared to confer protection against Graves' disease, whereas ApaI "aa" and TaqI "TT" genotypes were associated with an increased risk for Graves' disease. However, the true mechanisms of association remain to be elucidated.
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