title: Vitamin D 1alpha-hydroxylase (CYP1alpha) polymorphism in Graves' disease, Hashimoto's thyroiditis and type 1 diabetes mellitus.
abstract: OBJECTIVE
  The vitamin D endocrine system plays a role in the regulation of (auto)immunity and cell proliferation. Vitamin D 1alpha-hydroxylase (CYP1alpha) is one of the key enzymes regulating both systemic and tissue levels of 1,25-dihyroxyvitamin D(3) (1,25(OH)(2)D(3)). Administration of 1,25(OH)(2)D(3), whose serum levels were found to be reduced in type 1 diabetes and thyroid autoimmunity, prevents these diseases in animal models. We therefore investigated a recently reported CYP1alpha polymorphism for an association with type 1 diabetes mellitus, Graves' disease and Hashimoto's thyroiditis.
  
  
  METHODS
  Four hundred and seven Caucasian pedigrees with one offspring affected by either type 1 diabetes (209 families), Graves' disease (92 families) or Hashimoto's thyroiditis (106 families) were genotyped for a C/T polymorphism in intron 6 of the CYP1alpha gene on chromosome 12q13.1-13.3 and transmission disequilibrium testing (TDT) was performed. Subsets of affected offspring stratified for HLA-DQ haplotype were compared using chi(2) testing.
  
  
  RESULTS
  There was no deviation from the expected transmission frequency in either type 1 diabetes mellitus (P=0.825), Graves' disease (P=0.909) or Hashimoto's thyroiditis (P=0.204). However, in Hashimoto's thyroiditis the CYP1alpha C allele was significantly more often transmitted to HLA-DQ2(-) patients (27 transmitted vs 14 not transmitted; TDT: P=0.042) than expected. The C allele was less often transmitted to HLA-DQ2(+) patients (9 transmitted vs 12 not transmitted; TDT: P=0.513), although the difference was not significant (chi(2) test: P=0.143). A similar difference was observed in type 1 diabetes between offspring with high and low risk HLA-DQ haplotypes (chi(2) test: P=0.095).
  
  
  CONCLUSIONS
  The CYP1alpha intron 6 polymorphism appears not to be associated with type 1 diabetes mellitus, Graves' disease and Hashimoto's thyroiditis. A potential association in subsets of patients with type 1 diabetes and Hashimoto's thyroiditis should be further investigated as well as its functional implications.
authors.affiliation: Department of Internal Medicine I, Division of Endocrinology, University Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pani
authors.forename: Karoline
authors.initials: K
authors.lastname: Regulla
authors.forename: Maria
authors.initials: M
authors.lastname: Segni
authors.forename: Maren
authors.initials: M
authors.lastname: Krause
authors.forename: Stefan
authors.initials: S
authors.lastname: Hofmann
authors.forename: Michael
authors.initials: M
authors.lastname: Hufner
authors.forename: Jurgen
authors.initials: J
authors.lastname: Herwig
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Pasquino
authors.forename: Klaus-H
authors.initials: KH
authors.lastname: Usadel
authors.forename: Klaus
authors.initials: K
authors.lastname: Badenhoop
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D002117:Calcitriol / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics* / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005838:Genotype; D006111:Graves Disease / Q000235:genetics* / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013967:Thyroiditis, Autoimmune / Q000235:genetics* / Q000276:immunology
chemical_list: D006683:HLA-DQ Antigens; D019363:Cytochrome P-450 CYP1A1; D002117:Calcitriol