Predictive value of interleukin 1 gene polymorphisms for surgery

Anne Crilly, Nicola Maiden, Hilary A. Capell, Rajan Madhok

Research output: Contribution to journalArticle

Abstract

OBJECTIVES: To determine the influence of interleukin 1alpha (IL1alpha), IL1beta, and IL1 receptor antagonist gene polymorphisms on disease outcome as assessed by the need for major joint surgery within 15 years of diagnosis.

PATIENTS AND METHODS: 50 patients with rheumatoid arthritis (RA) who required major joint surgery (hip, knee, or shoulder arthroplasty) within a 15 year period of disease diagnosis and 50 patients with RA with disease duration greater than 15 years and no major surgery were recruited together with 66 normal west of Scotland controls. Genomic DNA and polymerase chain reaction were used to determine polymorphisms in the genes for IL1alpha, IL1beta, and IL1 receptor antagonist. For all patients with RA recruited to the study, HLA-DR beta1 gene status was recorded as was the erythrocyte sedimentation rate (ESR) at the first ever clinic visit.

RESULTS: No difference in the allele frequencies or genotypes of the IL1alpha and IL1 receptor antagonist gene polymorphisms was found between the controls and patients with RA, with or without previous surgery. IL1beta allele 2 was overrepresented in patients with RA who had undergone surgery compared with patients who had not (40% v 27%, chi(2)=4, 1df, p=0.04). ESR at the first ever clinic visit was significantly higher in those carrying allele 2 (36 mm/1st h v 22 mm/1st h, p=0.04). When patients, with or without previous surgery, who did not carry two disease associated HLA-DR beta1 alleles were compared, an increase in allele 2 was observed in the surgery cohort (42% v 25%, chi(2)=4.8, 1df, p=0.03).

CONCLUSIONS: Patients who require major joint surgery were found to carry the IL1beta allele 2 more often than expected. Patients with this allele also had a higher initial ESR. This may be useful in predicting early surgery in patients who do not carry two disease associated HLA-DR beta1 alleles. Although these findings are interesting, further functional and epidemiological studies to confirm these observations are required.

Original languageEnglish
Pages (from-to)695-699
Number of pages5
JournalAnnals of the Rheumatic Diseases
Volume59
Issue number9
DOIs
Publication statusPublished - 1 Sep 2000
Externally publishedYes

Fingerprint

Polymorphism
Interleukin-1
Surgery
Genes
Alleles
Rheumatoid Arthritis
Interleukin-1alpha
Interleukin-1 Receptors
HLA-DR Antigens
Blood Sedimentation
Sedimentation
Ambulatory Care
Joints
Interleukin Receptors
Arthroplasty
Polymerase chain reaction
DNA-Directed DNA Polymerase
Hip Joint
Scotland
Gene Frequency

Keywords

  • Aged
  • Alleles
  • Arthritis, Rheumatoid
  • Arthroplasty, Replacement
  • Blood Sedimentation
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease
  • HLA-DR Antigens
  • HLA-DRB1 Chains
  • Humans
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Prognosis
  • Retrospective Studies
  • Sialoglycoproteins

Cite this

Crilly, Anne ; Maiden, Nicola ; Capell, Hilary A. ; Madhok, Rajan. / Predictive value of interleukin 1 gene polymorphisms for surgery. In: Annals of the Rheumatic Diseases. 2000 ; Vol. 59, No. 9. pp. 695-699.
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abstract = "OBJECTIVES: To determine the influence of interleukin 1alpha (IL1alpha), IL1beta, and IL1 receptor antagonist gene polymorphisms on disease outcome as assessed by the need for major joint surgery within 15 years of diagnosis.PATIENTS AND METHODS: 50 patients with rheumatoid arthritis (RA) who required major joint surgery (hip, knee, or shoulder arthroplasty) within a 15 year period of disease diagnosis and 50 patients with RA with disease duration greater than 15 years and no major surgery were recruited together with 66 normal west of Scotland controls. Genomic DNA and polymerase chain reaction were used to determine polymorphisms in the genes for IL1alpha, IL1beta, and IL1 receptor antagonist. For all patients with RA recruited to the study, HLA-DR beta1 gene status was recorded as was the erythrocyte sedimentation rate (ESR) at the first ever clinic visit.RESULTS: No difference in the allele frequencies or genotypes of the IL1alpha and IL1 receptor antagonist gene polymorphisms was found between the controls and patients with RA, with or without previous surgery. IL1beta allele 2 was overrepresented in patients with RA who had undergone surgery compared with patients who had not (40{\%} v 27{\%}, chi(2)=4, 1df, p=0.04). ESR at the first ever clinic visit was significantly higher in those carrying allele 2 (36 mm/1st h v 22 mm/1st h, p=0.04). When patients, with or without previous surgery, who did not carry two disease associated HLA-DR beta1 alleles were compared, an increase in allele 2 was observed in the surgery cohort (42{\%} v 25{\%}, chi(2)=4.8, 1df, p=0.03).CONCLUSIONS: Patients who require major joint surgery were found to carry the IL1beta allele 2 more often than expected. Patients with this allele also had a higher initial ESR. This may be useful in predicting early surgery in patients who do not carry two disease associated HLA-DR beta1 alleles. Although these findings are interesting, further functional and epidemiological studies to confirm these observations are required.",
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Predictive value of interleukin 1 gene polymorphisms for surgery. / Crilly, Anne; Maiden, Nicola; Capell, Hilary A.; Madhok, Rajan.

In: Annals of the Rheumatic Diseases, Vol. 59, No. 9, 01.09.2000, p. 695-699.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Predictive value of interleukin 1 gene polymorphisms for surgery

AU - Crilly, Anne

AU - Maiden, Nicola

AU - Capell, Hilary A.

AU - Madhok, Rajan

PY - 2000/9/1

Y1 - 2000/9/1

N2 - OBJECTIVES: To determine the influence of interleukin 1alpha (IL1alpha), IL1beta, and IL1 receptor antagonist gene polymorphisms on disease outcome as assessed by the need for major joint surgery within 15 years of diagnosis.PATIENTS AND METHODS: 50 patients with rheumatoid arthritis (RA) who required major joint surgery (hip, knee, or shoulder arthroplasty) within a 15 year period of disease diagnosis and 50 patients with RA with disease duration greater than 15 years and no major surgery were recruited together with 66 normal west of Scotland controls. Genomic DNA and polymerase chain reaction were used to determine polymorphisms in the genes for IL1alpha, IL1beta, and IL1 receptor antagonist. For all patients with RA recruited to the study, HLA-DR beta1 gene status was recorded as was the erythrocyte sedimentation rate (ESR) at the first ever clinic visit.RESULTS: No difference in the allele frequencies or genotypes of the IL1alpha and IL1 receptor antagonist gene polymorphisms was found between the controls and patients with RA, with or without previous surgery. IL1beta allele 2 was overrepresented in patients with RA who had undergone surgery compared with patients who had not (40% v 27%, chi(2)=4, 1df, p=0.04). ESR at the first ever clinic visit was significantly higher in those carrying allele 2 (36 mm/1st h v 22 mm/1st h, p=0.04). When patients, with or without previous surgery, who did not carry two disease associated HLA-DR beta1 alleles were compared, an increase in allele 2 was observed in the surgery cohort (42% v 25%, chi(2)=4.8, 1df, p=0.03).CONCLUSIONS: Patients who require major joint surgery were found to carry the IL1beta allele 2 more often than expected. Patients with this allele also had a higher initial ESR. This may be useful in predicting early surgery in patients who do not carry two disease associated HLA-DR beta1 alleles. Although these findings are interesting, further functional and epidemiological studies to confirm these observations are required.

AB - OBJECTIVES: To determine the influence of interleukin 1alpha (IL1alpha), IL1beta, and IL1 receptor antagonist gene polymorphisms on disease outcome as assessed by the need for major joint surgery within 15 years of diagnosis.PATIENTS AND METHODS: 50 patients with rheumatoid arthritis (RA) who required major joint surgery (hip, knee, or shoulder arthroplasty) within a 15 year period of disease diagnosis and 50 patients with RA with disease duration greater than 15 years and no major surgery were recruited together with 66 normal west of Scotland controls. Genomic DNA and polymerase chain reaction were used to determine polymorphisms in the genes for IL1alpha, IL1beta, and IL1 receptor antagonist. For all patients with RA recruited to the study, HLA-DR beta1 gene status was recorded as was the erythrocyte sedimentation rate (ESR) at the first ever clinic visit.RESULTS: No difference in the allele frequencies or genotypes of the IL1alpha and IL1 receptor antagonist gene polymorphisms was found between the controls and patients with RA, with or without previous surgery. IL1beta allele 2 was overrepresented in patients with RA who had undergone surgery compared with patients who had not (40% v 27%, chi(2)=4, 1df, p=0.04). ESR at the first ever clinic visit was significantly higher in those carrying allele 2 (36 mm/1st h v 22 mm/1st h, p=0.04). When patients, with or without previous surgery, who did not carry two disease associated HLA-DR beta1 alleles were compared, an increase in allele 2 was observed in the surgery cohort (42% v 25%, chi(2)=4.8, 1df, p=0.03).CONCLUSIONS: Patients who require major joint surgery were found to carry the IL1beta allele 2 more often than expected. Patients with this allele also had a higher initial ESR. This may be useful in predicting early surgery in patients who do not carry two disease associated HLA-DR beta1 alleles. Although these findings are interesting, further functional and epidemiological studies to confirm these observations are required.

KW - Aged

KW - Alleles

KW - Arthritis, Rheumatoid

KW - Arthroplasty, Replacement

KW - Blood Sedimentation

KW - Case-Control Studies

KW - Female

KW - Genetic Predisposition to Disease

KW - HLA-DR Antigens

KW - HLA-DRB1 Chains

KW - Humans

KW - Interleukin 1 Receptor Antagonist Protein

KW - Interleukin-1

KW - Male

KW - Middle Aged

KW - Polymorphism, Genetic

KW - Prognosis

KW - Retrospective Studies

KW - Sialoglycoproteins

U2 - 10.1136/ard.59.9.695

DO - 10.1136/ard.59.9.695

M3 - Article

VL - 59

SP - 695

EP - 699

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

IS - 9

ER -