HLA alleles and IDDM in children in Hungary: a comparison with Finland.
It has been postulated that variation in the distribution of human leukocyte antigen (HLA)-encoded susceptibility alleles for insulin-dependent diabetes mellitus (IDDM) is the genetic basis for variation in the incidence of the disease between populations. The aim of this study was to characterize HLA-encoded susceptibility to IDDM in Hungary and to identify whether HLA-DRB1/DQ-encoded susceptibility could account for the five times lower incidence of disease in Hungary compared with Finland. The haplotypes DRB1*03-DQA1*05-DQB1*02 (DRB1*03-DQ2) and DRB1*04-DQA1*0301-DQB1*0302 (DRB1*04-DQ8) were significantly associated with disease in both populations. Three genotypes incorporating either or both of these haplotypes accounted for over 70% of the diabetic population in both races. The combined background frequency and the degree of risk as measured by odds ratios of these HLA-DRB1-DQ genotypes were not significantly different in the two countries. Comparison of the DRB1*0401-DQ8 haplotype between the two races suggested a role for HLA-B alleles in susceptibility. These data indicate that the susceptibility associated with high risk DRB1-DQ genotypes alone is insufficient to account for the fivefold variation in incidence of IDDM between Hungary and Finland. Other genetic and/or environmental influences must be involved.
Hermann
R
R
Department of Paediatrics, University Medical School of Pécs, Hungary.
Mijovic
C H
CH
Rayner
M
M
Croft
N
N
Kelly
M A
MA
Jenkins
D
D
Soltész
G
G
Barnett
A H
AH
D000483:Alleles; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D005260:Female; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D005838:Genotype; D006683:HLA-DQ Antigens / Q000145:classification / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000145:classification / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D015994:Incidence; D008297:Male; D012307:Risk Factors
D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen