한국인 그레이브스병 환자의 비타민 D 수용체 3′ 말단부위 유전자 다형성 = Vitamin D Receptor Gene 3′ End Polymorphisms in Patients with Graves` Disease in Koreans

국문 초록 (Abstract)

연구배경: 한국인 그레이브스병 환자를 대상으로 비타민 D 수용체 유전자 다형성을 조사하여 연관성을 살펴보고, 유전자형과 임상상 및 갑상선수용체자가항체 사이에 연관성이 있는지를 알아보고자 하였다.
방법: 새로 진단된 그레이브스병 환자 117명과 건강한 성인 156명을 대상으로 하였다. 비타민 D 수용체 3' 말단부위 유전자 다형성은 각각 ApaI, BsmI, TaqI 제한효소로 잘라 제한분절길이다형성 방법으로 유전자형을 비교 분석하였다. 절단부위가 존재하는 경우를 각각 a, b, t라 하였고, 존재하지 않는 경우를 A, B, T라 명명하였다.
결과: 제한효소 ApaI에 대한 유전자형의 분포는 각각 AA형 17.1%, Aa형 50.4%, aa형 32.5%이었고, BsmI의 경우는 BB형이 7.1%, Bb형이 35.4%, bb형이 57.5%이었고, TaqI 유전자형은 TT형이 92.6%, Tt형이 6.2%, tt형이 1.2%이었다. 이러한 분포는 정상인과 통계학적으로 유의한 차이를 보이지 않았다. 유전자형에 따른 그레이브스병 환자군의 임상상의 차이를 살펴보았을 때에, 모든 유전자형에서 연령, 성별, 갑상선종의 크기, 안구병증에는 유의한 차이를 보이지 않았다. aa유전자형에서 TBII(aa 55.9±18.3 vs. Aa 43.2±23.4, p<0.05; aa 55.9±18.3 vs. AA and Aa 42.9±23.5, p<0.05)와 WT-CHO TSAb (aa 620±829 vs. AA and Aa 353±306, p<0.05)가 높고, bb유전자형에서 Anti-thyroglobulin antibody가 높으며 (BB and Bb 31.9±38.9 vs. 51±42.8, p<0.05), b 유전자를 포함하는 군에서 혈청 alkaline phosphatase가 높은 결과를 보였다 (Bb and bb 139±68 vs. BB 82.2±15.5, p<0.05).
결론: 한국인에서 비타민 D 수용체 3' 말단부위의 유전자 다형성은 그레이브스병과 연관성이 없었다. 향후, 비타민 D 수용체 유전자와의 연관성을 확실히 규명하기 위해서는 3' 말단부위이외의 다른 부분의 유전자 다형성에 대한 연구가 필요할 것이다.

다국어 초록 (Multilingual Abstract)

Background: The aim of this study was to evaluate the association of vitamin D receptor (VDR) gene polymorphisms with Graves' disease in Koreans. We also investigated the association of VDR gene polymorphisms with the clinical characteristics and titers of TSH receptor antibodies in patients with Graves' disease.
Subjects and Methods: The VDR gene polymorphisms were evaluated in 117 patients with Graves' disease and 156 normal controls. The polymorphisms were represented according to restriction fragment length polymorphism; Aa(ApaI), Bb(BsmI), and Tt(TaqI), with the capital letters signifying the absence, and small letters the presence of restriction sites.
Results: The distribution of the ApaI polymorphism genotype was: AA(17.1%), Aa(50.4%)and aa(32.5%). The BsmI polymorphism genotype distribution was: BB(7.1%), Bb(35.4%) and bb(57.5%); and the TaqI polymorphism genotype distribution was: TT(92.6%), Tt(6.2) and tt(1.2%). No significant differences in either genotypic or allelic distributions were observed, between the patients with Graves' disease and the normal controls, associated with the VDR gene polymorphisms. No significant differences were observed with age, sex, size of goiter or the presence of ophthalmopathy, in patients with Graves' disease associated with the VDR gene polymorphisms. However, the titers of the TBII were significantly higher in the aa than the Aa genotype, and were also higher in the group without the A allele than in groups with(aa 55.9±18.3 vs. Aa 43.2±23.4, p<0.05; aa 55.9±18.3 vs. AA and Aa 42.9±23.5, p<0.05). Thyroid stimulating antibodies measured with a CHO cell transfected with a wild type of human TSH receptor, were also higher in patients without the A allele than in those with(aa 620±829 vs. AA and Aa 353±306, p<0.05). The titers of the anti-thyroglobulin antibodies were significantly higher in the groups not containing the B allele than in the group that did(bb 50.9±42.8 vs. BB and Bb 319.±38.9, p<0.05). The serum alkaline phosphatase activities were higher in the group having the b allele than in the group that did not(Bb and bb 139±68 vs. BB 82.2±15.5, p<0.05).
Conclusions: The VDR gene 3' end polymorphism was not associated with susceptibility to Graves' disease in Koreans. The studies of other polymorphism sites of the VDR gene might be required to elucidate the association of VDR gene polymorphism with Graves' disease in Koreans (J Kor Soc Endocrinol 18:12∼23, 2003).