A retroviral long terminal repeat adjacent to the HLA DQB1 gene (DQ-LTR13) modifies Type I diabetes susceptibility on high risk DQ haplotypes

Diabetologia
K BiedaK Badenhoop

Abstract

HLA-DQ genes, located in the human leukocyte antigen region on chromosome 6 p, are the main inherited factors predisposing to Type I (insulin-dependent) diabetes mellitus. Endogenous retroviral long-terminal repeats are integrated at several sites within this region, one of which is known to enhance susceptibility for Type I diabetes. We examined another LTR within the HLA-region as an additional genetic risk marker. We investigated the segregation of one long-terminal repeat (DQ-LTR13), located 1.3 kb upstream of HLA DQB1 with different HLA-DQ haplotypes, and its transmission to patients. A total of 284 Caucasian families (203 German and 81 Belgian) with at least one diabetic offspring were genotyped for DQA1, DQB1 and DQ-LTR13. DQ8/LTR13(+) was preferentially transmitted (139 transmitted vs 28 not transmitted; P(TDT) = 1.67 x 10(-14)) whereas no deviation from expected transmission frequencies was observed for DQ8/LTR13(-) (20 transmitted vs 17 not transmitted; P(TDT) = 1.00). DQ8/LTR13(+) alleles conferred a significantly higher risk for Type I diabetes than DQ8/LTR13(-) alleles (p chi(2) = 2.58 x 10(-14)). This difference remained significant even after DRB1 subtyping (p chi(2) = 0.02). Also, there was a significant differe...Continue Reading

Citations

Oct 25, 2002·Diabetes/metabolism Research and Reviews
Jul 20, 2010·International Reviews of Immunology·Eva BaladaJosep Ordi-Ros
Jan 1, 2006·Expert Review of Clinical Immunology·Antonina Dolei
Jul 1, 2008·Expert Review of Clinical Immunology·Alberto FalorniGiovanni Gambelunghe
Dec 4, 2004·The Journal of Allergy and Clinical Immunology·Mark S SchubertRaymond G Slavin

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