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Preliminary evidence that an endogenous retroviral long‐terminal repeat (LTR13) at the HLA‐DQB1 gene locus confers susceptibility to Addison's disease
Author(s) -
Pani Michael A.,
Seidl Christian,
Bieda Katrin,
Seissler Jochen,
Krause Maren,
Seifried Erhard,
Usadel KlausH.,
Badenhoop Klaus
Publication year - 2002
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1046/j.1365-2265.2002.t01-1-01548.x
Subject(s) - addison's disease , allele , linkage disequilibrium , human leukocyte antigen , long terminal repeat , haplotype , locus (genetics) , immunology , hla dr , genotype , biology , gene , disease , medicine , genetics , antigen , gene expression
Summary 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. DESIGN We investigated the role of LTR3 and LTR13, both of which are located adjacent to the DQB1 gene, in Addison's disease. PATIENTS 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.