Relationship between interleukin 6 promoter polymorphism at position -174, IL-6 serum levels, and the risk of relapse/recurrence in polymyalgia rheumatica

Luigi Boiardi, Bruno Casali, Enrico Farnetti, Nicolò Pipitone, Davide Nicoli, Fabrizio Cantini, Pierluigi Macchioni, Gianluigi Bajocchi, Maria Grazia Catanoso, Lia Pulsatelli, Dario Consonni, Carlo Salvarani

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Abstract

Objective. To assess the role of -174 G/C promoter polymorphism of interleukin 6 (IL-6) in the susceptibility to polymyalgia rheumatica (PMR). We also investigated whether this polymorphism modulates the circulating level of IL-6 and the risk of relapse/recurrence in a series of patients with PMR followed up prospectively. Methods. A prospective study of 112 consecutive, untreated patients with isolated PMR (i.e., without evidence of giant cell arteritis) who were followed up for at least 24 months. This cohort represented all patients diagnosed over a 5-year period in one Italian rheumatological secondary referral center. Patients were monitored for clinical signs/symptoms and acute-phase reactants. All PMR patients and 112 population-based controls from the same geographic area were genotyped for IL-6 polymorphism at position -174 by molecular methods, IL-6 serum levels were measured in 67 PMR patients and 43 population-based controls. Results. The distribution of the G/C 174 genotype was similar in PMR patients and controls. No significant associations with IL-6 promoter polymorphism at position -174 were found when PMR patients with and without relapse/recurrence were compared. Controls homozygous for the C allele had higher serum IL-6 levels than the carriers of the G allele (4.5 ± 3.7 pg/ml vs 1.8 ± 2.1 pg/ml, p = 0.01). Patients homolygous for the allele C had significantly higher values of IL-6 during followup than patients carrying GC or GG genotypes. CC homozygosity was significantly more frequent in patients with persistently elevated levels of IL-6 than in those without. The presence of persistently elevated IL-6 levels, but not the CC genotype, was associated with an increased frequency of relapse/recurrence. Conclusion. Our findings show that the 174 G/C promoter IL-6 polymorphism is not implicated in susceptibility to PMR. However, CC genotype characterized PMR patients with persistently elevated levels of IL-6 who are at higher risk of developing relapse/recurrence. A genetically modulated pattern of IL-6 production could affect the longterm outcome of patients with PMR.

Original languageEnglish
Pages (from-to)703-708
Number of pages6
JournalJournal of Rheumatology
Volume33
Issue number4
Publication statusPublished - Apr 2006

Fingerprint

Polymyalgia Rheumatica
Interleukin-6
Recurrence
Serum
Genotype
Population Control
Alleles
Secondary Care Centers
Giant Cell Arteritis
Acute-Phase Proteins
Signs and Symptoms

Keywords

  • Interleukin-6 polymorphism
  • Polymyalgia rheumatica
  • Relapse/recurrence
  • Serum interleukin-6 levels

ASJC Scopus subject areas

  • Rheumatology
  • Immunology

Cite this

Relationship between interleukin 6 promoter polymorphism at position -174, IL-6 serum levels, and the risk of relapse/recurrence in polymyalgia rheumatica. / Boiardi, Luigi; Casali, Bruno; Farnetti, Enrico; Pipitone, Nicolò; Nicoli, Davide; Cantini, Fabrizio; Macchioni, Pierluigi; Bajocchi, Gianluigi; Catanoso, Maria Grazia; Pulsatelli, Lia; Consonni, Dario; Salvarani, Carlo.

In: Journal of Rheumatology, Vol. 33, No. 4, 04.2006, p. 703-708.

Research output: Contribution to journalArticle

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title = "Relationship between interleukin 6 promoter polymorphism at position -174, IL-6 serum levels, and the risk of relapse/recurrence in polymyalgia rheumatica",
abstract = "Objective. To assess the role of -174 G/C promoter polymorphism of interleukin 6 (IL-6) in the susceptibility to polymyalgia rheumatica (PMR). We also investigated whether this polymorphism modulates the circulating level of IL-6 and the risk of relapse/recurrence in a series of patients with PMR followed up prospectively. Methods. A prospective study of 112 consecutive, untreated patients with isolated PMR (i.e., without evidence of giant cell arteritis) who were followed up for at least 24 months. This cohort represented all patients diagnosed over a 5-year period in one Italian rheumatological secondary referral center. Patients were monitored for clinical signs/symptoms and acute-phase reactants. All PMR patients and 112 population-based controls from the same geographic area were genotyped for IL-6 polymorphism at position -174 by molecular methods, IL-6 serum levels were measured in 67 PMR patients and 43 population-based controls. Results. The distribution of the G/C 174 genotype was similar in PMR patients and controls. No significant associations with IL-6 promoter polymorphism at position -174 were found when PMR patients with and without relapse/recurrence were compared. Controls homozygous for the C allele had higher serum IL-6 levels than the carriers of the G allele (4.5 ± 3.7 pg/ml vs 1.8 ± 2.1 pg/ml, p = 0.01). Patients homolygous for the allele C had significantly higher values of IL-6 during followup than patients carrying GC or GG genotypes. CC homozygosity was significantly more frequent in patients with persistently elevated levels of IL-6 than in those without. The presence of persistently elevated IL-6 levels, but not the CC genotype, was associated with an increased frequency of relapse/recurrence. Conclusion. Our findings show that the 174 G/C promoter IL-6 polymorphism is not implicated in susceptibility to PMR. However, CC genotype characterized PMR patients with persistently elevated levels of IL-6 who are at higher risk of developing relapse/recurrence. A genetically modulated pattern of IL-6 production could affect the longterm outcome of patients with PMR.",
keywords = "Interleukin-6 polymorphism, Polymyalgia rheumatica, Relapse/recurrence, Serum interleukin-6 levels",
author = "Luigi Boiardi and Bruno Casali and Enrico Farnetti and Nicol{\`o} Pipitone and Davide Nicoli and Fabrizio Cantini and Pierluigi Macchioni and Gianluigi Bajocchi and Catanoso, {Maria Grazia} and Lia Pulsatelli and Dario Consonni and Carlo Salvarani",
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T1 - Relationship between interleukin 6 promoter polymorphism at position -174, IL-6 serum levels, and the risk of relapse/recurrence in polymyalgia rheumatica

AU - Boiardi, Luigi

AU - Casali, Bruno

AU - Farnetti, Enrico

AU - Pipitone, Nicolò

AU - Nicoli, Davide

AU - Cantini, Fabrizio

AU - Macchioni, Pierluigi

AU - Bajocchi, Gianluigi

AU - Catanoso, Maria Grazia

AU - Pulsatelli, Lia

AU - Consonni, Dario

AU - Salvarani, Carlo

PY - 2006/4

Y1 - 2006/4

N2 - Objective. To assess the role of -174 G/C promoter polymorphism of interleukin 6 (IL-6) in the susceptibility to polymyalgia rheumatica (PMR). We also investigated whether this polymorphism modulates the circulating level of IL-6 and the risk of relapse/recurrence in a series of patients with PMR followed up prospectively. Methods. A prospective study of 112 consecutive, untreated patients with isolated PMR (i.e., without evidence of giant cell arteritis) who were followed up for at least 24 months. This cohort represented all patients diagnosed over a 5-year period in one Italian rheumatological secondary referral center. Patients were monitored for clinical signs/symptoms and acute-phase reactants. All PMR patients and 112 population-based controls from the same geographic area were genotyped for IL-6 polymorphism at position -174 by molecular methods, IL-6 serum levels were measured in 67 PMR patients and 43 population-based controls. Results. The distribution of the G/C 174 genotype was similar in PMR patients and controls. No significant associations with IL-6 promoter polymorphism at position -174 were found when PMR patients with and without relapse/recurrence were compared. Controls homozygous for the C allele had higher serum IL-6 levels than the carriers of the G allele (4.5 ± 3.7 pg/ml vs 1.8 ± 2.1 pg/ml, p = 0.01). Patients homolygous for the allele C had significantly higher values of IL-6 during followup than patients carrying GC or GG genotypes. CC homozygosity was significantly more frequent in patients with persistently elevated levels of IL-6 than in those without. The presence of persistently elevated IL-6 levels, but not the CC genotype, was associated with an increased frequency of relapse/recurrence. Conclusion. Our findings show that the 174 G/C promoter IL-6 polymorphism is not implicated in susceptibility to PMR. However, CC genotype characterized PMR patients with persistently elevated levels of IL-6 who are at higher risk of developing relapse/recurrence. A genetically modulated pattern of IL-6 production could affect the longterm outcome of patients with PMR.

AB - Objective. To assess the role of -174 G/C promoter polymorphism of interleukin 6 (IL-6) in the susceptibility to polymyalgia rheumatica (PMR). We also investigated whether this polymorphism modulates the circulating level of IL-6 and the risk of relapse/recurrence in a series of patients with PMR followed up prospectively. Methods. A prospective study of 112 consecutive, untreated patients with isolated PMR (i.e., without evidence of giant cell arteritis) who were followed up for at least 24 months. This cohort represented all patients diagnosed over a 5-year period in one Italian rheumatological secondary referral center. Patients were monitored for clinical signs/symptoms and acute-phase reactants. All PMR patients and 112 population-based controls from the same geographic area were genotyped for IL-6 polymorphism at position -174 by molecular methods, IL-6 serum levels were measured in 67 PMR patients and 43 population-based controls. Results. The distribution of the G/C 174 genotype was similar in PMR patients and controls. No significant associations with IL-6 promoter polymorphism at position -174 were found when PMR patients with and without relapse/recurrence were compared. Controls homozygous for the C allele had higher serum IL-6 levels than the carriers of the G allele (4.5 ± 3.7 pg/ml vs 1.8 ± 2.1 pg/ml, p = 0.01). Patients homolygous for the allele C had significantly higher values of IL-6 during followup than patients carrying GC or GG genotypes. CC homozygosity was significantly more frequent in patients with persistently elevated levels of IL-6 than in those without. The presence of persistently elevated IL-6 levels, but not the CC genotype, was associated with an increased frequency of relapse/recurrence. Conclusion. Our findings show that the 174 G/C promoter IL-6 polymorphism is not implicated in susceptibility to PMR. However, CC genotype characterized PMR patients with persistently elevated levels of IL-6 who are at higher risk of developing relapse/recurrence. A genetically modulated pattern of IL-6 production could affect the longterm outcome of patients with PMR.

KW - Interleukin-6 polymorphism

KW - Polymyalgia rheumatica

KW - Relapse/recurrence

KW - Serum interleukin-6 levels

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