A gene in the HLA class I region contributes to susceptibility to IDDM in the Finnish population View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1994-09

AUTHORS

M. Fennessy, K. Metcalfe, G. A. Hitman, M. Niven, P. A. Biro, J. Tuomilehto, E. Tuomilehto-Wolf, The Childhood Diabetes in Finland (DiMe) Study Group

ABSTRACT

In Finland the haplotype A2, Cw1, B56, DR4, DQ8 is the third most common haplotype in insulin-dependent diabetic (IDDM) patients and has the highest haplotype-specific absolute risk for IDDM. Cw1, B56, DR4, DQ8 haplotypes containing HLA-A alleles other than A2 are infrequent in the population and are not associated with IDDM. Comparison of the A2 and non-A2 haplotypes at the DNA level showed that they were identical at HLA-B,-DR, and -DQ loci. Evidence that class I alleles confer susceptibility to IDDM was obtained from the two HLA-C, -B, -DR and -DQ haplotypes most frequently found in IDDM patients in Finland. A24, A3 and A2 on the Cw3, B62, DR4, DQ8 haplotype, and A28, A2 and A1 on the Cw7, B8, DR3, DQ2 were all found to be associated with IDDM. In Finland these seven haplotypes, including A2, Cw1, B56, DR4, DQ8, account for 33% of diabetic haplotypes and 10.3% of non-diabetic haplotypes (p<0.00001). The contribution of the class I region to IDDM susceptibility was also apparent in those IDDM patients lacking the disease-predisposing class II alleles. Significantly more non-DR3/non-DR4 IDDM patients (47 of 55) possessed two of the IDDM-associated HLA-A alleles compared to non-DR3/non-DR4 control subjects (40 of 58; p=0.038). Moreover, IDDM patients confirmed by oligotyping as unable to form a ‘diabetes-susceptibility’ DQ heterodimer, tended to possess two diabetes-associated HLA-A alleles (12 of 13) compared to control subjects (12 of 20; p=0.056). More... »

PAGES

937-944

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/bf00400951

DOI

http://dx.doi.org/10.1007/bf00400951

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1002802208

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/7806025


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