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Tissue Antigens. 2011 Apr;77(4):338-40. doi: 10.1111/j.1399-0039.2011.01636.x.

No extreme genetic risk for type 1 diabetes among DR3/4-DQ8 siblings sharing both extended HLA haplotypes with their diabetic proband.

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Department of Immunohaematology & Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.


An extreme genetic risk for type 1 diabetes (T1D) was reported for DR3/4-DQ8 siblings sharing both extended human leukocyte antigen (HLA) haplotypes identical-by-descent (IBD) with their diabetic proband. We attempted to replicate this finding in our prospective Dutch T1D cohort and in families from the Type 1 Diabetes Genetics Consortium (T1DGC). Only 2 of the 14 Dutch siblings, sharing both DR3-DQ2/DR4-DQ8 haplotypes IBD with their diabetic proband, developed T1D in a 12-year follow-up period. No differential sharing of HLA haplotypes or significant transmission distortion in parents homozygous for HLA risk alleles was found in T1DGC material. Therefore, we could not confirm the reported extreme risk for T1D, suggesting that the risk conferred by other HLA complex loci is moderate.

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