Dataset Information

Interleukin 1 receptor antagonist (IL1RN) gene variants predict radiographic severity of knee osteoarthritis and risk of incident disease.

ABSTRACT: OBJECTIVE:In these studies, we examined the association of single nucleotide polymorphisms (SNPs) of the IL1RN gene with radiographic severity of symptomatic knee osteoarthritis (SKOA) and the risk of incident OA. We also explored these genetic polymorphisms in patients with new onset rheumatoid arthritis (RA). METHODS:Over 1000 subjects who met American College of Rheumatology criteria for tibiofemoral OA were selected from three independent, National Institute of Health (NIH)-funded cohorts. CTA and TTG haplotypes formed from three SNPs of the IL1RN gene (rs419598, rs315952, rs9005) were assessed for association with radiographic severity, and risk for incident radiographic OA (rOA) in a nested case-control cohort. These IL1RN haplotypes were also assessed for association with disease activity (DAS28) and plasma inflammatory markers in patients with RA. RESULTS:Carriage of the IL1RN TTG haplotype was associated with increased odds of more severe rOA compared with age-matched, sex-matched and body mass index-matched individuals. Examination of the osteoarthritis initiative Incidence Subcohort demonstrated that carriage of the TTG haplotype was associated with 4.1-fold (p=0.001) increased odds of incident rOA. Plasma IL-1Ra levels were lower in TTG carriers, while chondrocytes from TTG carriers exhibited decreased secretion of IL-1Ra. In patients with RA, the TTG haplotype was associated with increased DAS28, decreased plasma IL-1Ra and elevations of plasma inflammatory markers (hsCRP, interleukin 6 (IL-6)). CONCLUSION:Carriage of the IL1RN TTG haplotype is associated with more severe rOA, increased risk for incident OA, and increased evidence of inflammation in RA. These data suggest that the IL1RN TTG risk haplotype, associated with decreased IL-1Ra plasma levels, impairs endogenous 'anti-inflammatory' mechanisms.

SUBMITTER: Attur M

PROVIDER: S-EPMC7034355 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Interleukin 1 receptor antagonist (<i>IL1RN</i>) gene variants predict radiographic severity of knee osteoarthritis and risk of incident disease.

Attur Mukundan M Zhou Hua H Samuels Johathan J Krasnokutsky Svetlana S Yau Michelle M Scher Jose U JU Doherty Michael M Wilson Anthony G AG Bencardino Jenny J Hochberg Marc M Jordan Joanne M JM Mitchell Braxton B Kraus Virginia B VB Abramson Steven B SB

Annals of the rheumatic diseases 20191218 3

<h4>Objective</h4>In these studies, we examined the association of single nucleotide polymorphisms (SNPs) of the <i>IL1RN</i> gene with radiographic severity of symptomatic knee osteoarthritis (SKOA) and the risk of incident OA. We also explored these genetic polymorphisms in patients with new onset rheumatoid arthritis (RA).<h4>Methods</h4>Over 1000 subjects who met American College of Rheumatology criteria for tibiofemoral OA were selected from three independent, National Institute of Health ( ...[more]

PMID: 31852669

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Project description:Importance:Persons with knee symptoms recognize the health benefits of engaging in physical activity, but uncertainty persists about whether regular strenuous physical activity or exercise can accelerate tissue damage. A sedentary lifestyle of inactivity or underloading may also be associated with deleterious joint health. Objective:To establish whether long-term strenuous physical activity participation and extensive sitting behavior are each associated with increased risk of developing radiographic knee osteoarthritis (KOA) in individuals at high risk for the disease. Design, Setting, and Participants:This cohort study analyzed data from the Osteoarthritis Initiative, a prospective longitudinal cohort study of men and women with or at an increased risk of developing symptomatic, radiographic KOA. Community-dwelling adults were recruited from 4 US sites (Baltimore, Maryland; Columbus, Ohio; Pittsburgh, Pennsylvania; and Pawtucket, Rhode Island) and were followed up for up to 10 years. Individuals were included if they had a baseline Kellgren and Lawrence grade of 0 in both knees and completed a PASE (Physical Activity Scale for the Elderly) questionnaire at baseline and at least 2 follow-up visits over an 8-year interval. Data analyses were conducted from May 2018 to November 2018. Exposures:Baseline to 8-year trajectories of strenuous physical activity participation and extensive sitting behavior were identified using group-based trajectory models. Main Outcomes and Measures:Incident radiographic KOA, defined as Kellgren and Lawrence grade 2 or higher in either knee by the 10-year follow-up visit. Results:A total of 1194 participants were included in the sample (697 women [58.4%]), with a baseline mean (SD) age of 58.4 (8.9) years and mean body mass index (BMI) of 26.8 (4.5). Four distinct trajectories of weekly hours spent in strenuous physical activities and 3 distinct trajectories of extensive sitting were identified. Long-term engagement in low-to-moderate physical activities (adjusted odds ratio [OR], 0.69; 95% CI, 0.48-1.01) or any strenuous physical activities (adjusted OR, 0.75; 95% CI, 0.53-1.07) was not associated with 10-year incident radiographic KOA. Persistent extensive sitting was not associated with incident KOA. Despite relatively mild symptoms and high function in this early-stage sample, 594 participants (49.7%) did not engage in any strenuous physical activities (ie, 0 h/wk) across 8 years, and 507 (42.5%) engaged in persistent moderate-to-high frequency of extensive sitting. Older age, higher BMI, more severe knee pain, non-college graduate educational level, weaker quadriceps, and depression were each associated with a persistent lack of engagement in strenuous physical activities. Conclusions and Relevance:Results from this study appeared to show no association between long-term strenuous physical activity participation and incident radiographic KOA. The findings raise the possibility of a protective association between incident KOA and a low-to-moderate level of strenuous physical activities.

Dataset Information

Interleukin 1 receptor antagonist (IL1RN) gene variants predict radiographic severity of knee osteoarthritis and risk of incident disease.

Publications

Interleukin 1 receptor antagonist (<i>IL1RN</i>) gene variants predict radiographic severity of knee osteoarthritis and risk of incident disease.

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