Associations of toll-like receptor (TLR)-4 single nucleotide polymorphisms and rheumatoid arthritis disease progression: An observational cohort study

Marshall L R Davis, Tricia D LeVan, Fang Yu, Harlan Sayles, Jeremy Sokolove, William Robinson, Kaleb D Michaud, Geoffrey Milton Thiele, Ted R Mikuls

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Abstract

Objective To examine the associations of toll-like receptor (TLR)-4 single nucleotide polymorphisms (SNPs) with disease progression in rheumatoid arthritis (RA). Methods A total of 1188 RA patients were genotyped for TLR4 SNPs (rs1927911, rs11536878, and rs4986790). Measures of disease activity were examined, including Disease Activity Score-28 (DAS28), Multidimensional Health Assessment Questionnaire (MD-HAQ), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI). Genetic associations with these longitudinal measures were examined using generalized estimating equations in both univariate and multivariate analyses. Analyses were then stratified by antigen specific anti-citrullinated peptide antibody (ACPA) status including antibody to citrullinated fibrinogen and citrullinated histone H2B. Results Disease activity measures progressed less over time in the homozygous minor allele group of rs1927911 including DAS28 (p < 0.001), CDAI (p = 0.008), and MD-HAQ (p = 0.015) in univariate analysis and DAS28, CDAI and SDAI in multivariate analysis. Disease activity progression among those homozygous for the minor allele tended to be lower in the groups with positive ACPA though major differences by autoantibody status were not identified. There were no associations of TLR4 rs11536878 and rs4986790 SNPs with RA disease activity progression. Conclusions In this population, TLR4 rs1927911 genotypes are associated with disease activity independent of other covariates.

Original languageEnglish (US)
Pages (from-to)346-352
Number of pages7
JournalInternational Immunopharmacology
Volume24
Issue number2
DOIs
StatePublished - Feb 2015

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Toll-Like Receptor 4
Observational Studies
Single Nucleotide Polymorphism
Disease Progression
Rheumatoid Arthritis
Cohort Studies
Antibodies
Multivariate Analysis
Alleles
Peptides
Health
Autoantibodies
Histones
Fibrinogen
Genotype

Keywords

  • Disease activity
  • Disease progression
  • Disease severity
  • Rheumatoid arthritis
  • Single nucleotide polymorphisms
  • Toll-like receptor (TLR)-4

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

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title = "Associations of toll-like receptor (TLR)-4 single nucleotide polymorphisms and rheumatoid arthritis disease progression: An observational cohort study",
abstract = "Objective To examine the associations of toll-like receptor (TLR)-4 single nucleotide polymorphisms (SNPs) with disease progression in rheumatoid arthritis (RA). Methods A total of 1188 RA patients were genotyped for TLR4 SNPs (rs1927911, rs11536878, and rs4986790). Measures of disease activity were examined, including Disease Activity Score-28 (DAS28), Multidimensional Health Assessment Questionnaire (MD-HAQ), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI). Genetic associations with these longitudinal measures were examined using generalized estimating equations in both univariate and multivariate analyses. Analyses were then stratified by antigen specific anti-citrullinated peptide antibody (ACPA) status including antibody to citrullinated fibrinogen and citrullinated histone H2B. Results Disease activity measures progressed less over time in the homozygous minor allele group of rs1927911 including DAS28 (p < 0.001), CDAI (p = 0.008), and MD-HAQ (p = 0.015) in univariate analysis and DAS28, CDAI and SDAI in multivariate analysis. Disease activity progression among those homozygous for the minor allele tended to be lower in the groups with positive ACPA though major differences by autoantibody status were not identified. There were no associations of TLR4 rs11536878 and rs4986790 SNPs with RA disease activity progression. Conclusions In this population, TLR4 rs1927911 genotypes are associated with disease activity independent of other covariates.",
keywords = "Disease activity, Disease progression, Disease severity, Rheumatoid arthritis, Single nucleotide polymorphisms, Toll-like receptor (TLR)-4",
author = "Davis, {Marshall L R} and LeVan, {Tricia D} and Fang Yu and Harlan Sayles and Jeremy Sokolove and William Robinson and Michaud, {Kaleb D} and Thiele, {Geoffrey Milton} and Mikuls, {Ted R}",
year = "2015",
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T1 - Associations of toll-like receptor (TLR)-4 single nucleotide polymorphisms and rheumatoid arthritis disease progression

T2 - An observational cohort study

AU - Davis, Marshall L R

AU - LeVan, Tricia D

AU - Yu, Fang

AU - Sayles, Harlan

AU - Sokolove, Jeremy

AU - Robinson, William

AU - Michaud, Kaleb D

AU - Thiele, Geoffrey Milton

AU - Mikuls, Ted R

PY - 2015/2

Y1 - 2015/2

N2 - Objective To examine the associations of toll-like receptor (TLR)-4 single nucleotide polymorphisms (SNPs) with disease progression in rheumatoid arthritis (RA). Methods A total of 1188 RA patients were genotyped for TLR4 SNPs (rs1927911, rs11536878, and rs4986790). Measures of disease activity were examined, including Disease Activity Score-28 (DAS28), Multidimensional Health Assessment Questionnaire (MD-HAQ), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI). Genetic associations with these longitudinal measures were examined using generalized estimating equations in both univariate and multivariate analyses. Analyses were then stratified by antigen specific anti-citrullinated peptide antibody (ACPA) status including antibody to citrullinated fibrinogen and citrullinated histone H2B. Results Disease activity measures progressed less over time in the homozygous minor allele group of rs1927911 including DAS28 (p < 0.001), CDAI (p = 0.008), and MD-HAQ (p = 0.015) in univariate analysis and DAS28, CDAI and SDAI in multivariate analysis. Disease activity progression among those homozygous for the minor allele tended to be lower in the groups with positive ACPA though major differences by autoantibody status were not identified. There were no associations of TLR4 rs11536878 and rs4986790 SNPs with RA disease activity progression. Conclusions In this population, TLR4 rs1927911 genotypes are associated with disease activity independent of other covariates.

AB - Objective To examine the associations of toll-like receptor (TLR)-4 single nucleotide polymorphisms (SNPs) with disease progression in rheumatoid arthritis (RA). Methods A total of 1188 RA patients were genotyped for TLR4 SNPs (rs1927911, rs11536878, and rs4986790). Measures of disease activity were examined, including Disease Activity Score-28 (DAS28), Multidimensional Health Assessment Questionnaire (MD-HAQ), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI). Genetic associations with these longitudinal measures were examined using generalized estimating equations in both univariate and multivariate analyses. Analyses were then stratified by antigen specific anti-citrullinated peptide antibody (ACPA) status including antibody to citrullinated fibrinogen and citrullinated histone H2B. Results Disease activity measures progressed less over time in the homozygous minor allele group of rs1927911 including DAS28 (p < 0.001), CDAI (p = 0.008), and MD-HAQ (p = 0.015) in univariate analysis and DAS28, CDAI and SDAI in multivariate analysis. Disease activity progression among those homozygous for the minor allele tended to be lower in the groups with positive ACPA though major differences by autoantibody status were not identified. There were no associations of TLR4 rs11536878 and rs4986790 SNPs with RA disease activity progression. Conclusions In this population, TLR4 rs1927911 genotypes are associated with disease activity independent of other covariates.

KW - Disease activity

KW - Disease progression

KW - Disease severity

KW - Rheumatoid arthritis

KW - Single nucleotide polymorphisms

KW - Toll-like receptor (TLR)-4

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