HLA haplotype analysis in Finnish patients with rheumatoid arthritis

J Tuokko, S Nejentsev, R Luukkainen, A Toivanen, J Ilonen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

OBJECTIVE: To further characterize the HLA gene products that play an important role in the pathogenesis of rheumatoid arthritis (RA).

METHODS: 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.

RESULTS: 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 < 0.001). The DRB1*13-associated DQB1*0604 allele was similarly decreased in RA haplotypes (P = 0.025). The TAP2I allele of I/J dimorphism was increased in RA patients (85%, or 114 of 134) as compared with controls (69%, or 49 of 71) (P = 0.011). Of the tumor necrosis factor (TNF) microsatellite alleles, TNFa6 and TNFb5 were found to be increased in RA haplotypes (for a6 27% versus 5% in controls [P = 0.00043], and for b5 43% versus 26% in controls [P = 0.037]).

CONCLUSION: Both protection-associated and susceptibility-associated alleles can be found among HLA class II genes, and the results suggest that loci outside DR/DQ may contribute to the pathogenesis of RA.

Original languageEnglish
Pages (from-to)315-22
Number of pages8
JournalArthritis and Rheumatism
Volume44
Issue number2
DOIs
Publication statusPublished - Feb 2001

Cite this

Tuokko, J ; Nejentsev, S ; Luukkainen, R ; Toivanen, A ; Ilonen, J. / HLA haplotype analysis in Finnish patients with rheumatoid arthritis. In: Arthritis and Rheumatism. 2001 ; Vol. 44, No. 2. pp. 315-22.
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abstract = "OBJECTIVE: To further characterize the HLA gene products that play an important role in the pathogenesis of rheumatoid arthritis (RA).METHODS: 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.RESULTS: 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 < 0.001). The DRB1*13-associated DQB1*0604 allele was similarly decreased in RA haplotypes (P = 0.025). The TAP2I allele of I/J dimorphism was increased in RA patients (85{\%}, or 114 of 134) as compared with controls (69{\%}, or 49 of 71) (P = 0.011). Of the tumor necrosis factor (TNF) microsatellite alleles, TNFa6 and TNFb5 were found to be increased in RA haplotypes (for a6 27{\%} versus 5{\%} in controls [P = 0.00043], and for b5 43{\%} versus 26{\%} in controls [P = 0.037]).CONCLUSION: Both protection-associated and susceptibility-associated alleles can be found among HLA class II genes, and the results suggest that loci outside DR/DQ may contribute to the pathogenesis of RA.",
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HLA haplotype analysis in Finnish patients with rheumatoid arthritis. / Tuokko, J; Nejentsev, S; Luukkainen, R; Toivanen, A; Ilonen, J.

In: Arthritis and Rheumatism, Vol. 44, No. 2, 02.2001, p. 315-22.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - HLA haplotype analysis in Finnish patients with rheumatoid arthritis

AU - Tuokko, J

AU - Nejentsev, S

AU - Luukkainen, R

AU - Toivanen, A

AU - Ilonen, J

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N2 - OBJECTIVE: To further characterize the HLA gene products that play an important role in the pathogenesis of rheumatoid arthritis (RA).METHODS: 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.RESULTS: 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 < 0.001). The DRB1*13-associated DQB1*0604 allele was similarly decreased in RA haplotypes (P = 0.025). The TAP2I allele of I/J dimorphism was increased in RA patients (85%, or 114 of 134) as compared with controls (69%, or 49 of 71) (P = 0.011). Of the tumor necrosis factor (TNF) microsatellite alleles, TNFa6 and TNFb5 were found to be increased in RA haplotypes (for a6 27% versus 5% in controls [P = 0.00043], and for b5 43% versus 26% in controls [P = 0.037]).CONCLUSION: Both protection-associated and susceptibility-associated alleles can be found among HLA class II genes, and the results suggest that loci outside DR/DQ may contribute to the pathogenesis of RA.

AB - OBJECTIVE: To further characterize the HLA gene products that play an important role in the pathogenesis of rheumatoid arthritis (RA).METHODS: 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.RESULTS: 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 < 0.001). The DRB1*13-associated DQB1*0604 allele was similarly decreased in RA haplotypes (P = 0.025). The TAP2I allele of I/J dimorphism was increased in RA patients (85%, or 114 of 134) as compared with controls (69%, or 49 of 71) (P = 0.011). Of the tumor necrosis factor (TNF) microsatellite alleles, TNFa6 and TNFb5 were found to be increased in RA haplotypes (for a6 27% versus 5% in controls [P = 0.00043], and for b5 43% versus 26% in controls [P = 0.037]).CONCLUSION: Both protection-associated and susceptibility-associated alleles can be found among HLA class II genes, and the results suggest that loci outside DR/DQ may contribute to the pathogenesis of RA.

KW - Arthritis, Rheumatoid/epidemiology

KW - Child

KW - Family Health

KW - Female

KW - Finland/epidemiology

KW - HLA-DP Antigens/genetics

KW - HLA-DR Antigens/genetics

KW - HLA-DRB1 Chains

KW - Haplotypes

KW - Humans

KW - Microsatellite Repeats/genetics

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DO - 10.1002/1529-0131(200102)44:2<315::AID-ANR48>3.0.CO;2-G

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