Preliminary evidence that an endogenous retroviral long-terminal repeat (LTR13) at the HLA-DQB1 gene locus confers susceptibility to Addison's disease.

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. [ABSTRACT FROM AUTHOR]