Hla‐dr alleles with naturally occurring amino acid substitutions and risk for development of rheumatoid arthritis

Xiaojiang Gao, Nancy Olsen, Theodore Pincus, Peter Stastny

Research output: Contribution to journalArticle

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Abstract

To determine the HLA‐DR4 subtypes associated with rheumatoid arthritis (RA), we performed amplification of DR4 DRB1 genes by the polymerase chain reaction and dot‐blots with oligonucleotide probes. In 52 HLA‐DR4+ RA patients, Dw4 was the predominant subtype. This subtype was found in 45 of 52 patients (86.5%) compared with 33 of 59 DR4+ controls (55.9%; P < 0.001). In the whole population, Dw4 also gave the highest relative risk for RA (RR = 5.31). Relative risk was also associated with DR1.1, the common white DR1 (Dw1) type, which has a third hypervariable region amino acid sequence similar to some forms of DR4 and has glycine at position 86. Variants of DR1 (DR1.2) or DR4 (Dw14.1, Dw14.1) with valine at position 86 appeared less able to confer risk for RA. Substitution of residues in the third hypervariable region of the first domain of DRB1 appeared to correlate with relative risk for RA. Among subjects having 0–1 amino acid substitutions, RA developed in 53%, whereas in subjects with 2–4 amino acid changes, RA was present in only 17.4% (P < 0.00001). DQw7 (formerly DQw3.1) was slightly increased in DR4+ RA patients compared with controls, but a striking excess of Dw4,DQw7 homozygous patients was observed. The results suggest that DQw7 may have an additional effect, possibly with a recessive mechanism, since it was observed only in DR4 homozygous patients.

Original languageEnglish (US)
Pages (from-to)939-946
Number of pages8
JournalArthritis & Rheumatism
Volume33
Issue number7
DOIs
StatePublished - Jan 1 1990

Fingerprint

Amino Acid Substitution
Rheumatoid Arthritis
Alleles
Oligonucleotide Probes
Valine
Glycine
Amino Acid Sequence
Amino Acids
Polymerase Chain Reaction
Population
Genes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

Cite this

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title = "Hla‐dr alleles with naturally occurring amino acid substitutions and risk for development of rheumatoid arthritis",
abstract = "To determine the HLA‐DR4 subtypes associated with rheumatoid arthritis (RA), we performed amplification of DR4 DRB1 genes by the polymerase chain reaction and dot‐blots with oligonucleotide probes. In 52 HLA‐DR4+ RA patients, Dw4 was the predominant subtype. This subtype was found in 45 of 52 patients (86.5{\%}) compared with 33 of 59 DR4+ controls (55.9{\%}; P < 0.001). In the whole population, Dw4 also gave the highest relative risk for RA (RR = 5.31). Relative risk was also associated with DR1.1, the common white DR1 (Dw1) type, which has a third hypervariable region amino acid sequence similar to some forms of DR4 and has glycine at position 86. Variants of DR1 (DR1.2) or DR4 (Dw14.1, Dw14.1) with valine at position 86 appeared less able to confer risk for RA. Substitution of residues in the third hypervariable region of the first domain of DRB1 appeared to correlate with relative risk for RA. Among subjects having 0–1 amino acid substitutions, RA developed in 53{\%}, whereas in subjects with 2–4 amino acid changes, RA was present in only 17.4{\%} (P < 0.00001). DQw7 (formerly DQw3.1) was slightly increased in DR4+ RA patients compared with controls, but a striking excess of Dw4,DQw7 homozygous patients was observed. The results suggest that DQw7 may have an additional effect, possibly with a recessive mechanism, since it was observed only in DR4 homozygous patients.",
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Hla‐dr alleles with naturally occurring amino acid substitutions and risk for development of rheumatoid arthritis. / Gao, Xiaojiang; Olsen, Nancy; Pincus, Theodore; Stastny, Peter.

In: Arthritis & Rheumatism, Vol. 33, No. 7, 01.01.1990, p. 939-946.

Research output: Contribution to journalArticle

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