The effect of HLA-B allele on the IDDM risk defined by DRB1*04 subtypes and DQB1*0302

被引:56
作者
Nejentsev, S
Reijonen, H
Adojaan, B
Kovalchuk, L
Sochnevs, A
Schwartz, EI
Akerblom, HK
Ilonen, J
机构
[1] UNIV TURKU,DEPT VIROL,FIN-20520 TURKU,FINLAND
[2] UNIV TURKU,TURKU IMMUNOL CTR,FIN-20520 TURKU,FINLAND
[3] PEDIAT MED ACAD,DEPT MED GENET,ST PETERSBURG,RUSSIA
[4] TARTU UNIV HOSP,DEPT ENDOCRINOL,TARTU,ESTONIA
[5] LATVIAN MED ACAD,LAB IMMUNOGENET & IMMUNOL,RIGA,LATVIA
[6] UNIV HELSINKI,CHILDRENS HOSP,HELSINKI,FINLAND
关键词
D O I
10.2337/diabetes.46.11.1888
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The genes encoding the HLA-DQ heterodimer molecules, DQB1 and DQA1, have been found to have the strongest association with IDDM risk, although there is cumulative evidence for the effect of other gene loci within the major histocompatibility complex gene region, After the HLA-DQ locus, the HLA-DR locus has been suggested most often as contributing to the disease susceptibility, In this study we analyzed at the population level the effect of DR4 subtypes and class I, HLA-B alleles, on IDDM risk when the influence of the Do locus was stratified, In all three populations studied (Estonian, Latvian, and Russian), DQB1-0302 haplotypes most frequently carried DRB1-0401 or DRB1-0404, DRB1-0401 was the most prevalent subtype in IDDM patients, whereas DRB1-0404 was decreased in frequency, DRB1-0402 was also prevalent among Russian haplotypes, but was not associated with IDDM risk, When HLA-B alleles were analyzed, strong associations between the presence of specific B alleles and DRB1-04 subtypes were detected, The HLA-B39 allele was found significantly more often in DRB1-0404-DQB1-0302-positive patients than in healthy control subjects positive for this haplotype: 27 of 54 (50%) vs, 4 of 49 (8.2%) (P < 0.0001), The results demonstrate that DQ and DR genes cannot explain all of the HLA-linked susceptibility to IDDM, and that the existence of a susceptibility locus telomeric to DR is probable.
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页码:1888 / 1892
页数:5
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