Document Detail


IL-1B and IL-1RN gene polymorphisms in rheumatoid arthritis: relationship with protein plasma levels and response to therapy.
MedLine Citation:
PMID:  16886894     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: To analyze the association of interleukin (IL-1) gene polymorphisms with susceptibility to, and severity of, rheumatoid arthritis (RA) patients, comparing them with the genotype distribution in healthy controls. Also, to assess the influence of IL1-B and IL1RN gene polymorphism on IL-1beta/IL-1Ra plasma levels and response to therapy. PATIENTS AND METHODS: We tested the allelic distribution of IL-1B (-511 and +3953) and IL-1RN (variable number of tandem repeats) gene polymorphism in 126 RA patients and 178 healthy blood donors (HBDs). The patients were categorized into two subgroups in relation to the response to methotrexate (MTX) therapy. Group A included 70 RA patients in stable partial remission after 6 months of MTX treatment (MTX-R). Group B included 56 RA patients with active disease despite MTX therapy. This group received antitumor necrosis factor (TNF) biological drugs and were defined MTX-nonresponders (MTX-NR). RESULTS: None of the two IL-1B (-511 and +3953) gene polymorphisms were significantly different in frequency between RA patients and healthy controls. We observed an increased frequency of the rare allele IL1RN*3 in RA patients with active disease, not responding to MTX therapy (MTX-NR) (4.5%) vs MTX-R (3.6%) and healthy controls (0.8%). Interestingly, RA patients whose genotypes included the IL1RN*long allele (haplotype long-C-T) showed the worse response to MTX. HBDs harboring the IL1RN*2/2 genotype showed significantly lower levels of plasma IL1-Ra, but comparable levels of IL-1beta with regard to subjects with the presence of the IL1RN* long allele. Furthermore, the presence of the TT IL-1B +3953 genotype was associated with lower plasma levels of IL1-Ra, both in HBDs and in RA patients. Carriers of the IL1RN*2 allele responded better to infliximab therapy. CONCLUSIONS: The results of this study provide evidence of an association between the IL1RN*long allele and RA, the strongest association being observed in RA patients with an aggressive disease resistant to MTX treatment.
Authors:
Barbara Tolusso; Donatello Pietrapertosa; Alessia Morelli; Maria De Santis; Elisa Gremese; Giuseppina Farina; Siro Giorgio Carniello; Marino Del Frate; Gianfranco Ferraccioli
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Pharmacogenomics     Volume:  7     ISSN:  1462-2416     ISO Abbreviation:  Pharmacogenomics     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-08-04     Completed Date:  2006-10-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100897350     Medline TA:  Pharmacogenomics     Country:  England    
Other Details:
Languages:  eng     Pagination:  683-95     Citation Subset:  IM    
Affiliation:
UCSC-Catholic University of Rome, Division of Rheumatology, 00168 Rome, Italy.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Alleles
Arthritis, Rheumatoid / blood*,  drug therapy,  genetics*
Female
Humans
Interleukin 1 Receptor Antagonist Protein
Interleukin-1 / blood,  genetics*
Male
Methotrexate / therapeutic use*
Middle Aged
Polymorphism, Genetic / genetics*
Sialoglycoproteins / blood,  genetics*
Chemical
Reg. No./Substance:
0/IL1RN protein, human; 0/Interleukin 1 Receptor Antagonist Protein; 0/Interleukin-1; 0/Sialoglycoproteins; 59-05-2/Methotrexate

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