title: Association between copy number variation of complement component C4 and Graves' disease.
abstract: BACKGROUND
  Gene copy number of complement component C4, which varies among individuals, may determine the intrinsic strength of the classical complement pathway. Presuming a major role of complement as an effecter in peptide-mediated inflammation and phagocytosis, we hypothesized that C4 genetic diversity may partially explain the development of Graves' disease (GD) and the variation in its outcomes.
  
  
  METHODS
  A case-control study including 624 patients with GD and 160 healthy individuals were enrolled. CNV of C4 isotypes (C4A and C4B) genes were performed by quantitative real-time polymerase chain reaction analysis. Statistical comparison and identification of CNV of total C4, C4 isotypes (C4A and C4B) and C4 polymorphisms were estimated according to the occurrence of GD and its associated clinical features.
  
  
  RESULTS
  Individuals with 4, 2, and 2 copies of C4, C4A and C4B genes, especially those with A2B2 polymorphism may associate with the development of GD (p = 0.001, OR = 10.994, 95% CI: 6.277-19.255; p = 0.008, OR = 1.732, 95% CI: 1.190-2.520; p = 2.420 × 10-5, OR = 2.621, 95% CI: 1.791-3.835; and p = 1.395 × 10-4, OR = 2.671, 95% CI: 1.761-4.052, respectively). Although the distribution of copy number for total C4, C4 isotypes as well as C4 polymorphisms did not associate with the occurrence of goiter, nodular hyperplasia, GO and myxedema, <2 copies of C4A may associate with high risk toward vitiligo in patients with GD (p = 0.001, OR = 5.579, 95% CI: 1.659-18.763).
  
  
  CONCLUSIONS
  These results may be further estimated for its clinical application on GD and the vitiligo in patients with GD.
authors.affiliation: Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung, Taiwan. d0704@mail.cmuh.org.tw.
authors.forename: Yu-Huei
authors.initials: YH
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Wan
authors.forename: Chwen-Tzuei
authors.initials: CT
authors.lastname: Chang
authors.forename: Wen-Ling
authors.initials: WL
authors.lastname: Liao
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Chen
authors.forename: Yuhsin
authors.initials: Y
authors.lastname: Tsai
authors.forename: Chang-Hai
authors.initials: CH
authors.lastname: Tsai
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003181:Complement C4 / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006042:Goiter / Q000235:genetics; D006111:Graves Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009230:Myxedema / Q000235:genetics; D011110:Polymorphism, Genetic; D020033:Protein Isoforms / Q000235:genetics*; D012307:Risk Factors; D014820:Vitiligo / Q000235:genetics
chemical_list: D003181:Complement C4; D020033:Protein Isoforms