Non-class II HLA gene associated with type 1 diabetes maps to the 240-kb region near HLA-B

S Nejentsev, Z Gombos, A P Laine, R Veijola, M Knip, O Simell, O Vaarala, H K Akerblom, J Ilonen

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Abstract

Several studies provide evidence that in addition to the DQ-DR genes, HLA contains another uncharacterized gene or genes associated with type 1 diabetes. Our aim was to investigate the effect of this gene independently of the DQ-DR genes and to localize it with a matched case-control study. More than 1,400 patients and 30,000 control individuals from Finland were studied. They were first genotyped for the selected alleles of the HLA-DQB1, -DQA1, and -DRB1 genes. For the DR3/4(0404) genotype, 75 patients and 181 control subjects were stratified, and 241 patients and 354 controls were stratified for the DR3/4(0401) genotype. Ten microsatellite markers in the HLA class III and I regions (D6S273, TNFa, C12A, STR MICA, MIB, C125, C143, C245, C3211, and MOGc) and selected alleles of the HLA-A and HLA-B genes were studied. In the DR3/4(0404)-stratified group, we found that markers located between C12A and C143 near the HLA-B gene confer a strong additional diabetes association. This was confirmed by the population differentiation test in both DR3/4(0404)- and DR3/4(0401)-stratified groups. Our data indicate that an additional gene associated with type 1 diabetes is located in the 240-kb region near HLA-B. We excluded STR MICA polymorphism as a mutation responsible for diabetes association.

Original languageEnglish
Pages (from-to)2217-21
Number of pages5
JournalDiabetes
Volume49
Issue number12
Publication statusPublished - Dec 2000

Cite this

Nejentsev, S., Gombos, Z., Laine, A. P., Veijola, R., Knip, M., Simell, O., ... Ilonen, J. (2000). Non-class II HLA gene associated with type 1 diabetes maps to the 240-kb region near HLA-B. Diabetes, 49(12), 2217-21.