HLA-DRB1-ASTERISK-0401 IS ASSOCIATED WITH SUSCEPTIBILITY TO INSULIN-DEPENDENT DIABETES-MELLITUS INDEPENDENTLY OF THE DQB1 LOCUS

Tait, BD; DRUMMOND, BP; Varney, MD; Harrison, LC

Author(s): Tait, BD; DRUMMOND, BP; Varney, MD; Harrison, LC;
Details: Publication Year 1995-08,Volume 22,Issue #4,Page 289-297
Journal Title: EUROPEAN JOURNAL OF IMMUNOGENETICS
Publication Type: Journal Article
Abstract: The distribution of DRB1*04 alleles and DRB1/DQB1 haplotypes was analysed in 57 DR4(+) caucasoid subjects with insulin-dependent diabetes mellitus (IDDM) and 96 DR4(+) healthy controls selected on the basis of DR serology, and the findings were analysed in relation to age at diagnosis of IDDM. DNA samples were amplified using specific DR and DQ primers and hybridized with sequence-specific oligonucleotide probes. A significantly increased combined frequency of DRB1*0401 and 0402 was observed in IDDM subjects aged less than or equal to 12 years at diagnosis (allele frequency 88.4% compared with 62.0% in controls, P < 0.025). There was a non-significant increase in DRB1*0401 and 0402 in IDDM subjects less than or equal to 12 years when compared with IDDM subjects > 12 years (P < 0.1). DRB1*0404 was decreased in the total IDDM subject group compared with controls (4.8% vs. 19.0%, P < 0.025) but did not reach statistical significance in the individual age at diagnosis groups. In contrast, the frequency of DQB1*0302 was increased uniformly across both ages at diagnosis groups. In controls DRB1*0401 occurred in haplotype. association with DQB1*0301 in a significantly greater frequency than with DQB1*0302. However, 95.0% of DRB1*0401 IDDM subjects were DQB1*0302. DRB1*0404, which was decreased in frequency in IDDM subjects, occurred in association significantly more frequently with DQB1*0302 in controls. These results imply that DRB1 and DQB1 have independent roles as HLA susceptibility genes in IDDM. DQB1 may have a permissive role whereas DRB1 could influence the rate at which underlying disease progresses to clinical IDDM.
Publisher: BLACKWELL SCIENCE LTD
Keywords: HLA-DQ; BETA-CHAIN; ASPARTIC-ACID; GENETIC SUSCEPTIBILITY; T-CELLS; IDDM; POSITION-57; JAPANESE; COMBINATION; SEQUENCE
Publisher's Version: https://doi.org/10.1111/j.1744-313X.1995.tb00245.x
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 1995-08-01 12:00:00