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HLA-DR4 subtype and -B alleles in DQB1*0302-positive haplotypes associated with IDDM. The Childhood Diabetes in Finland Study Group.

https://arctichealth.org/en/permalink/ahliterature206798
Source
Eur J Immunogenet. 1997 Oct;24(5):357-63
Publication Type
Article
Date
Oct-1997
Author
H. Reijonen
S. Nejentsev
J. Tuokko
S. Koskinen
E. Tuomilehto-Wolf
H K Akerblom
J. Ilonen
Author Affiliation
Turku Immunology Centre, University of Turku, Finland.
Source
Eur J Immunogenet. 1997 Oct;24(5):357-63
Date
Oct-1997
Language
English
Publication Type
Article
Keywords
Adolescent
Alleles
Child
Child, Preschool
Diabetes Mellitus, Type 1 - epidemiology - genetics - immunology
Disease Susceptibility
Finland - epidemiology
Gene Frequency
Genetic Linkage
HLA-B Antigens - analysis - genetics
HLA-DQ Antigens - genetics
HLA-DQ beta-Chains
HLA-DR Antigens - analysis - genetics
HLA-DR4 Antigen - analysis - genetics
HLA-DRB1 Chains
Haplotypes - genetics
Humans
Risk factors
Abstract
We determined the distribution of DR4 subtypes in 309 DQB1*0302-positive haplotypes found in insulin-dependent diabetes mellitus (IDDM) patients and 70 control haplotypes present only in healthy family members. An increased frequency of DRB1*0401 allele (74.4% vs. 55.7%, P = 0.003) and a decrease of DRB1*0404 allele (23.6% vs. 40.0%, P = 0.0064) was revealed. A further analysis of extended haplotypes demonstrated strong linkages between various B alleles and DRB1*04 subtypes. HLA-B39 was more frequent in DRB1*0404-DQB1*0302-positive IDDM haplotypes compared with control ones (37.0% vs. 14.3%, P = 0.049), suggesting an involvement of the region telomeric to HLA-DRB1 in the susceptibility to IDDM.
PubMed ID
9442803 View in PubMed
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HLA-DR-DQ haplotypes and genotypes in Finnish patients with rheumatoid arthritis.

https://arctichealth.org/en/permalink/ahliterature177977
Source
Ann Rheum Dis. 2004 Nov;63(11):1406-12
Publication Type
Article
Date
Nov-2004
Author
S. Laivoranta-Nyman
T. Möttönen
R. Hermann
J. Tuokko
R. Luukkainen
M. Hakala
P. Hannonen
M. Korpela
U. Yli-Kerttula
A. Toivanen
J. Ilonen
Author Affiliation
Turku Immunology Centre, University of Turku, Tykistökatu 6A, FIN-20520 Turku, Finland. susanna.laivoranta-nyman@utu.fi
Source
Ann Rheum Dis. 2004 Nov;63(11):1406-12
Date
Nov-2004
Language
English
Publication Type
Article
Keywords
Arthritis, Rheumatoid - genetics - immunology
Case-Control Studies
Chi-Square Distribution
Female
Finland
Gene Frequency
Genes, MHC Class II
Genetic Predisposition to Disease
Genotype
HLA-DQ Antigens - genetics
HLA-DR Antigens - genetics
Haplotypes
Humans
Male
Models, Genetic
Risk
Abstract
To elucidate the contribution of HLA-DR-DQ haplotypes and their genotypic combinations to susceptibility to rheumatoid arthritis, and to evaluate the various models for HLA associated risk for the disease in a series of Finnish patients.
322 Finnish patients with rheumatoid arthritis were typed for common north European HLA-DR-DQ haplotypes and compared with a series of 1244 artificial family based control haplotypes.
The association of the so called shared epitope (SE) haplotypes (DRB1*0401, *0404, *0408, and *01) with rheumatoid arthritis was confirmed. The DRB1*0401 haplotypes carried a far stronger risk for the disease than the (DRB1*01/10)-(DQA1*01)-DQB1*0501 haplotypes. Seven protective HLA haplotypes--(DRB1*15)-(DQA1*01)-DQB1*0602; (DRB1*08)-(DQA1*04)-DQB1*04; (DRB1*11/12)-DQA1*05-DQB1*0301; (DRB1*1301)-(DQA1*01)-DQB1*0603; (DRB1*1302)-(DQA1*01)-DQB1*0604; (DRB1*07)-DQA1*0201-DQB1*0303; and (DRB1*16)- (DQA1*01)-DQB1*0502--were identified. In accordance with the reshaped shared epitope hypothesis, all the protective DRB1 alleles in these haplotypes share either isoleucine at position 67 or aspartic acid at position 70 in their third hypervariable region motif. However, differences in the disease risk of haplotypes carrying the same DR but different DQ alleles were also found: (DRB1*07)-DQA1*0201-DQB1*0303 was protective, while (DRB1*07)-DQA1*0201-DQB1*02 was neutral. The same haplotypes carried different risks for rheumatoid arthritis depending on their combination in genotypes.
When assessing the influence of HLA genes on the susceptibility to rheumatoid arthritis, not only should the HLA-DR or -DQ alleles or haplotypes be unravelled but also the genotype. The effect of HLA class II region genes is more complicated than any of the existing hypotheses can explain.
Notes
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Comment In: Ann Rheum Dis. 2005 Apr;64(4):655; author reply 65515769932
PubMed ID
15479890 View in PubMed
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HLA haplotype analysis in Finnish patients with rheumatoid arthritis.

https://arctichealth.org/en/permalink/ahliterature195543
Source
Arthritis Rheum. 2001 Feb;44(2):315-22
Publication Type
Article
Date
Feb-2001
Author
J. Tuokko
S. Nejentsev
R. Luukkainen
A. Toivanen
J. Ilonen
Author Affiliation
Department of Medical Microbiology, University of Turku, Finland.
Source
Arthritis Rheum. 2001 Feb;44(2):315-22
Date
Feb-2001
Language
English
Publication Type
Article
Keywords
Arthritis, Rheumatoid - epidemiology - genetics
Child
Family Health
Female
Finland - epidemiology
HLA-DP Antigens - genetics
HLA-DR Antigens - genetics
HLA-DRB1 Chains
Haplotypes
Humans
Microsatellite Repeats - genetics
Abstract
To further characterize the HLA gene products that play an important role in the pathogenesis of rheumatoid arthritis (RA).
One hundred thirty-four haplotypes from 67 Finnish RA patients and 77 control haplotypes were analyzed for HLA-DRB1 loci, associated alleles of the HLA-DQB1 locus, alleles of the type 2 transporter-associated antigen processing (TAP2) genes, and HLA-B27. In addition, a panel of microsatellite markers within the HLA class I and class III regions was studied.
The frequency of HLA-DRB1*04 in the haplotypes of RA patients was found to be 34% (45 of 134) compared with 14% (10 of 72) in control haplotypes (P = 0.004). The frequency of HLA-DRB1*13 was decreased in RA haplotypes (4%, or 5 of 134) in contrast to control haplotypes (24%, or 17 of 72) (P = 0.000031). The decrease in DRB1*13 was not secondary to the increase in DRB1*04, since it was also found among DRB1*04-negative haplotypes (P
PubMed ID
11229461 View in PubMed
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