title: Association of vitamin D receptor gene polymorphism with susceptibility to Graves' disease in Eastern Croatian population: case-control study.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nuclear Medicine and Radiation Protection, University Hospital Osijek, J. Huttlera 4, 31000 Osijek, Croatia. stefanic.mario@kbo.hr
authors.forename: Mario
authors.initials: M
authors.lastname: Stefanić
authors.forename: Ivan
authors.initials: I
authors.lastname: Karner
authors.forename: Ljubica
authors.initials: L
authors.lastname: Glavas-Obrovac
authors.forename: Stana
authors.initials: S
authors.lastname: Papić
authors.forename: Dubravka
authors.initials: D
authors.lastname: Vrdoljak
authors.forename: Gordana
authors.initials: G
authors.lastname: Levak
authors.forename: Branislav
authors.initials: B
authors.lastname: Krstonosić
mesh_terms: D000328:Adult; D001483:Base Sequence; D016022:Case-Control Studies; D017523:Croatia; D017931:DNA Primers; D005260:Female; D020022:Genetic Predisposition to Disease; D006111:Graves Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics*
chemical_list: D017931:DNA Primers; D018167:Receptors, Calcitriol