title: Preliminary evidence that an endogenous retroviral long-terminal repeat (LTR13) at the HLA-DQB1 gene locus confers susceptibility to Addison's disease.
abstract: OBJECTIVE
  Addison's disease is associated with particular haplotypes of the human leucocyte antigen (HLA) region [DQA1*0501-DQB1*0201 (DQ2) and DQA1*0301-DQB1*0302 (DQ8)]. This locus harbours several human endogenous retroviral (HERV) long-terminal repeats (LTR). LTRs within the HLA region have been shown to confer additional susceptibility to type 1 diabetes and rheumatoid arthritis.
  
  
  METHODS
  We investigated the role of LTR3 and LTR13, both of which are located adjacent to the DQB1 gene, in Addison's disease.
  
  
  METHODS
  Eighty-seven patients and 160 controls were genotyped for HLA-DQA, -DQB, and the presence or absence of LTR3 and LTR13.
  
  
  RESULTS
  Significantly more patients' HLA alleles than those of controls carried the LTR13 insertion (19.0% vs. 10.6%, P = 0.0143), whereas there was only a trend for LTR3 (allele-wise chi-squared test: P = 0.0941). Both, LTR3 and LTR13 are in strong linkage disequilibrium with DQ8, which itself was significantly more frequent in patients than in controls (29.9% vs. 15.0%, P = 0.0089). However, significantly more alleles of DQ8+ patients than of DQ8+ controls carried the LTR13 insertion (44.2% vs. 18.8%, P = 0.0119), whereas we did not observe any difference for LTR3 in the DQ8+ subset (30.5 vs. 23.1%, P = 0.9416).
  
  
  CONCLUSIONS
  We have found preliminary evidence that the endogenous retroviral element DQ-LTR13, but not LTR3, is associated with Addison's disease. LTR13 appears to enhance HLA-DQ8 mediated disease risk. This retroviral insertion therefore might represent a novel susceptibility factor in Addison's disease, but these findings need to be confirmed in a larger data set.
authors.affiliation: Department of Internal Medicine I, University Hospital, Frankfurt am Main, Germany.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pani
authors.forename: Christian
authors.initials: C
authors.lastname: Seidl
authors.forename: Katrin
authors.initials: K
authors.lastname: Bieda
authors.forename: Jochen
authors.initials: J
authors.lastname: Seissler
authors.forename: Maren
authors.initials: M
authors.lastname: Krause
authors.forename: Erhard
authors.initials: E
authors.lastname: Seifried
authors.forename: Klaus-H
authors.initials: KH
authors.lastname: Usadel
authors.forename: Klaus
authors.initials: K
authors.lastname: Badenhoop
mesh_terms: D000224:Addison Disease / Q000235:genetics* / Q000821:virology; D000293:Adolescent; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006801:Humans; D016254:Mutagenesis, Insertional; D016133:Polymerase Chain Reaction; D012190:Retroviridae / Q000235:genetics; D020079:Terminal Repeat Sequences
chemical_list: D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen