Diabetes, Vol 40, Issue 6 748-753, Copyright © 1991 by American Diabetes Association
HLA-DQA1 and -DQB1 alleles associated with genetic susceptibility to IDDM in a black population
CH Mijovic, D Jenkins, KH Jacobs, MA Penny, JA Fletcher and AH Barnett
Department of Medicine, University of Birmingham, United Kingdom.
Transracial analysis provides a method of distinguishing primary
associations between insulin-dependent diabetes mellitus (IDDM) and HLA
class II alleles from those secondary to linkage disequilibrium. Blacks
show DR-DQ relationships that are different from other races and are a
useful group in which to investigate HLA-D region associations with IDDM.
In this study, the frequencies of HLA-DQA1 and -DQB1 alleles in
Afro-Caribbean IDDM and control subjects were compared. Alleles were
identified with sequence-specific oligonucleotide probing. The DQA1 allele
A3 was positively associated with IDDM (relative risk [RR] = 25.3,
corrected P [Pc] less than 7.0 x 10(-6). The DQB1 alleles DQw2 and DQw8
were also positively associated (RR = 4.7, Pc less than 6.5 x 10(-3) and RR
= 12.3, Pc = 3.4 x 10(-3), respectively). The A1.2 and DQw6 alleles were
negatively associated (RR = 0.16, Pc less than 3.5 x 10(-3) and RR = 0.15,
Pc = 2.4 x 10(-2), respectively). These findings were compared to data from
other races. The positive associations with A3 and DQw2 are consistent with
all racial groups investigated. The negative association with DQw6 is
present in all racial groups in which it is a common allele. These findings
suggest that DQ alleles, and hence DQ molecules, may directly affect
predisposition to IDDM.