Preliminary evidence that an endogenous retroviral long-terminal repeat (LTR13) at the HLA-DQB1 gene locus confers susceptibility to Addison's disease.
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.
Pani
Michael A
MA
Department of Internal Medicine I, University Hospital, Frankfurt am Main, Germany.
Seidl
Christian
C
Bieda
Katrin
K
Seissler
Jochen
J
Krause
Maren
M
Seifried
Erhard
E
Usadel
Klaus-H
KH
Badenhoop
Klaus
K
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
D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen