Rheumatoid arthritis in Israeli Jews

Shared sequences in the third hypervariable region of DRB1 alleles are associated with susceptibility

X. Gao, E. Gazit, A. Livneh, P. Stastny

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Rheumatoid arthritis (RA) is known to be associated with class HLA antigens in most populations, but recent studies in Israeli Jewish patients showed no significant differences in either DR4 or DR1 between patients and controls. In a previous DR4 subset study we found DR4-Dw15 to be associated with susceptibility (RR = 9.2) but this allele occurred in only 12% of the patients. We analyzed all DRB1 genes, using the polymerase chain reaction (PCR) and hybridization with allele specific oligonucleotides, in 49 Jewish patients with RA and 40 normal Jewish controls. Six DRB1 alleles that are similar to the prototype DR4-Dw4 (DRB1*0401) appeared to contribute to the risk for developing RA. In addition to DR4-Dw15 (DRB1*0405) 2 other alleles having substitutions in codons 71 only (DR1-Dw1/DRB1*0101, DR4-Dw14.2/DRB1*0408) or in codons 70 and 71 (DRw10/DRB1*1001) gave highly significant relative risks. Together, this group, with valine in position 85, and glycine in codon 86, gave a relative risk of 11.0 (p = 0.0002). Two other alleles with the same sequence in the third hypervariable region (amino acids 67-74) but with valine in codon 86 (DR4-Dw14.1/DRB1*0404) or alanine in 85 and valine in 86 (DR1-Dw20, DRB1*0102) gave a combined risk of 3.6 (p = 0.049). Altogether these 7 alleles with similar sequences in the third hypervariable region accounted for 55.6% of the patients, with an overall relative risk of 8.6 (p = 0.00002). Our results in this population indicate that shared epitopes in the third hypervariable region of DRB1 alleles also play a role in susceptibility to RA. The strong association with DRw10 appears to be unique for this ethnic group.

Original languageEnglish (US)
Pages (from-to)801-803
Number of pages3
JournalJournal of Rheumatology
Volume18
Issue number6
StatePublished - 1991

Fingerprint

Jews
Rheumatoid Arthritis
Alleles
Codon
Valine
HLA Antigens
Ethnic Groups
Oligonucleotides
Alanine
Glycine
Population
Epitopes
Amino Acids
Polymerase Chain Reaction
Genes

Keywords

  • HLA alleles
  • hybridization
  • Israeli jews
  • oligonucleotide
  • rheumatoid arthritis

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

Rheumatoid arthritis in Israeli Jews : Shared sequences in the third hypervariable region of DRB1 alleles are associated with susceptibility. / Gao, X.; Gazit, E.; Livneh, A.; Stastny, P.

In: Journal of Rheumatology, Vol. 18, No. 6, 1991, p. 801-803.

Research output: Contribution to journalArticle

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abstract = "Rheumatoid arthritis (RA) is known to be associated with class HLA antigens in most populations, but recent studies in Israeli Jewish patients showed no significant differences in either DR4 or DR1 between patients and controls. In a previous DR4 subset study we found DR4-Dw15 to be associated with susceptibility (RR = 9.2) but this allele occurred in only 12{\%} of the patients. We analyzed all DRB1 genes, using the polymerase chain reaction (PCR) and hybridization with allele specific oligonucleotides, in 49 Jewish patients with RA and 40 normal Jewish controls. Six DRB1 alleles that are similar to the prototype DR4-Dw4 (DRB1*0401) appeared to contribute to the risk for developing RA. In addition to DR4-Dw15 (DRB1*0405) 2 other alleles having substitutions in codons 71 only (DR1-Dw1/DRB1*0101, DR4-Dw14.2/DRB1*0408) or in codons 70 and 71 (DRw10/DRB1*1001) gave highly significant relative risks. Together, this group, with valine in position 85, and glycine in codon 86, gave a relative risk of 11.0 (p = 0.0002). Two other alleles with the same sequence in the third hypervariable region (amino acids 67-74) but with valine in codon 86 (DR4-Dw14.1/DRB1*0404) or alanine in 85 and valine in 86 (DR1-Dw20, DRB1*0102) gave a combined risk of 3.6 (p = 0.049). Altogether these 7 alleles with similar sequences in the third hypervariable region accounted for 55.6{\%} of the patients, with an overall relative risk of 8.6 (p = 0.00002). Our results in this population indicate that shared epitopes in the third hypervariable region of DRB1 alleles also play a role in susceptibility to RA. The strong association with DRw10 appears to be unique for this ethnic group.",
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AB - Rheumatoid arthritis (RA) is known to be associated with class HLA antigens in most populations, but recent studies in Israeli Jewish patients showed no significant differences in either DR4 or DR1 between patients and controls. In a previous DR4 subset study we found DR4-Dw15 to be associated with susceptibility (RR = 9.2) but this allele occurred in only 12% of the patients. We analyzed all DRB1 genes, using the polymerase chain reaction (PCR) and hybridization with allele specific oligonucleotides, in 49 Jewish patients with RA and 40 normal Jewish controls. Six DRB1 alleles that are similar to the prototype DR4-Dw4 (DRB1*0401) appeared to contribute to the risk for developing RA. In addition to DR4-Dw15 (DRB1*0405) 2 other alleles having substitutions in codons 71 only (DR1-Dw1/DRB1*0101, DR4-Dw14.2/DRB1*0408) or in codons 70 and 71 (DRw10/DRB1*1001) gave highly significant relative risks. Together, this group, with valine in position 85, and glycine in codon 86, gave a relative risk of 11.0 (p = 0.0002). Two other alleles with the same sequence in the third hypervariable region (amino acids 67-74) but with valine in codon 86 (DR4-Dw14.1/DRB1*0404) or alanine in 85 and valine in 86 (DR1-Dw20, DRB1*0102) gave a combined risk of 3.6 (p = 0.049). Altogether these 7 alleles with similar sequences in the third hypervariable region accounted for 55.6% of the patients, with an overall relative risk of 8.6 (p = 0.00002). Our results in this population indicate that shared epitopes in the third hypervariable region of DRB1 alleles also play a role in susceptibility to RA. The strong association with DRw10 appears to be unique for this ethnic group.

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