Genetic heterogeneity of insulin-dependent (type I) diabetes mellitus: evidence from a study of extended haplotypes.

Abstract:

:Two hundred subjects with insulin-dependent (type I) diabetes mellitus (IDDM) were typed for HLA-B, HLA-DR, and properdin factor B (Bf). HLA and Bf antigen and haplotype frequencies in subjects were compared with control frequencies derived from the 8th HLA Workshop. Frequencies of extended haplotypes (defined by B-Bf-DR alleles on a chromosome) were also contrasted with control frequencies. Significant positive associations between IDDM and HLA-B8, DR3, DR4, BfS, and BfF1 were confirmed, as were significant negative associations between IDDM and HLA-B7, DR2, DR5, DR7, and BfF. One haplotype (B7-BfS-DR2) exhibited significant negative association, while five haplotypes (B8-BfS-DR3, B8-BfS-DR4, B15-BfS-DR4, B18-BfF1-DR3, and B40-BfS-DR4) exhibited significant positive associations with IDDM. In this sample, 64% of all probands carried at least one of the high-risk haplotypes. In conclusion, the occurrence of five "high-risk" haplotypes associated with IDDM provides evidence for previously undocumented genetic heterogeneity and suggests that possibly more than two HLA-region genes may be involved in IDDM susceptibility.

journal_name

Am J Hum Genet

authors

Rich SS,Weitkamp LR,Barbosa J

subject

Has Abstract

pub_date

1984-09-01 00:00:00

pages

1015-23

issue

5

eissn

0002-9297

issn

1537-6605

journal_volume

36

pub_type

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