Stefanić Mario, Karner Ivan, Glavas-Obrovac Ljubica, Papić Stana, Vrdoljak Dubravka, Levak Gordana, Krstonosić Branislav
Department of Nuclear Medicine and Radiation Protection, University Hospital Osijek, J. Huttlera 4, 31000 Osijek, Croatia.
Croat Med J. 2005 Aug;46(4):639-46.
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.
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.
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).
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.
评估维生素D3受体（VDR）基因BsmI/ApaI/TaqI限制性片段长度多态性对克罗地亚东部部分患者Graves病易感性的影响。
对110例Graves病患者和99例种族匹配的甲状腺功能正常对照者进行基因分型，这些对照者无甲状腺或自身免疫性疾病的临床证据或家族史。采用序列特异性引物进行聚合酶链反应扩增后，通过BsmI/ApaI/TaqI内切酶消化对VDR基因多态性进行基因分型。数据采用卡方检验分析，并计算粗比值比（OR）及95%置信区间（95%CI）。
患者中ApaI “AA”基因型（分别为14.5%对30.3%，患者对对照，OR = 0.39，95%CI [0.2 - 0.77]，P = 0.01）和BsmI “BB”基因型（7.3%对23.2%，OR = 0.26 [0.11 - 0.61]，P = 0.002）的比例明显低于对照；而患者中ApaI “aa”基因型（28.2%对9.1%，OR = 3.92 [1.76 - 8.74]，P = 0.001）和TaqI “TT”基因型（51.8%对31.3%，OR = 2.36 [1.34 - 4.16]，P = 0.004）的比例明显高于对照。对Graves病具有最强保护作用的基因型组合是“BBAAtt”（2.7%对17.2%，OR = 0.14 [0.04 - 0.48]，P = 0.001）。
这些发现表明，VDR基因BsmI/ApaI/TaqI多态性与克罗地亚东部部分患者的Graves病易感性相关。ApaI和BsmI的“AA”和“BB”基因型以及组合的“BBAAtt”基因型似乎对Graves病具有保护作用，而ApaI “aa”和TaqI “TT”基因型与Graves病风险增加相关。然而，真正的关联机制仍有待阐明。
