TY - JOUR

T1 - Smoking and polymorphisms of genes encoding mannose-binding lectin and surfactant protein-D in patients with rheumatoid arthritis

AU - Kristiansen, Malthe

AU - Frisch, Morten

AU - Madsen, Hans Ole

AU - Garred, Peter

AU - Jacobsen, Søren

PY - 2014/3

Y1 - 2014/3

N2 - To investigate whether polymorphisms in genes coding for mannose-binding lectin (MBL) and surfactant protein-D (SP-D) are associated directly or by interaction with smoking with rheumatoid arthritis (RA), anti-citrullinated peptide antibody (ACPA) positive RA, and erosive RA. MBL2 genotypes, SFTPD genotype at codon 11, and HLA-shared epitope were determined in 456 patients with rheumatoid arthritis and 533 sex- and age-matched controls. Patients were grouped according to the presence of ACPA antibodies and RA-associated bone erosions and sub-stratified according to smoking status as never or ever smokers. Odds ratios with 95% confidence interval (OR, 95% CI) were calculated using multiple logistic regression analyses controlling for shared epitope. The low-producing SFTPD genotype was not associated with risk of RA or ACPA positive RA, but with erosive disease in the RA patients (OR = 1.8; 95% CI 1.1-3.0) particularly in RA ever smokers (OR = 2.4; 95% CI 1.3-4.3). The high-producing MBL2 genotype YA/YA was associated with ACPA positive RA (OR = 1.4; 95% CI 1.0-1.9) and erosive joint disease in RA ever smokers (OR = 1.8; 95% CI 1.1-3.0). Genetic disposition for low SP-D was not associated with RA but with erosive RA by interaction with smoking. The genetic disposition for high MBL production was associated with ACPA positive RA irrespective of shared epitope. The findings need to be replicated but do as such offer further explanations for the clinical heterogeneity of RA.

AB - To investigate whether polymorphisms in genes coding for mannose-binding lectin (MBL) and surfactant protein-D (SP-D) are associated directly or by interaction with smoking with rheumatoid arthritis (RA), anti-citrullinated peptide antibody (ACPA) positive RA, and erosive RA. MBL2 genotypes, SFTPD genotype at codon 11, and HLA-shared epitope were determined in 456 patients with rheumatoid arthritis and 533 sex- and age-matched controls. Patients were grouped according to the presence of ACPA antibodies and RA-associated bone erosions and sub-stratified according to smoking status as never or ever smokers. Odds ratios with 95% confidence interval (OR, 95% CI) were calculated using multiple logistic regression analyses controlling for shared epitope. The low-producing SFTPD genotype was not associated with risk of RA or ACPA positive RA, but with erosive disease in the RA patients (OR = 1.8; 95% CI 1.1-3.0) particularly in RA ever smokers (OR = 2.4; 95% CI 1.3-4.3). The high-producing MBL2 genotype YA/YA was associated with ACPA positive RA (OR = 1.4; 95% CI 1.0-1.9) and erosive joint disease in RA ever smokers (OR = 1.8; 95% CI 1.1-3.0). Genetic disposition for low SP-D was not associated with RA but with erosive RA by interaction with smoking. The genetic disposition for high MBL production was associated with ACPA positive RA irrespective of shared epitope. The findings need to be replicated but do as such offer further explanations for the clinical heterogeneity of RA.

KW - Adolescent

KW - Adult

KW - Aged

KW - Antibodies, Anti-Idiotypic

KW - Arthritis, Rheumatoid

KW - Case-Control Studies

KW - Epitopes

KW - Female

KW - Genotype

KW - Haplotypes

KW - Humans

KW - Male

KW - Mannose-Binding Lectin

KW - Middle Aged

KW - Peptides, Cyclic

KW - Polymorphism, Genetic

KW - Pulmonary Surfactant-Associated Protein D

KW - Retrospective Studies

KW - Risk Factors

KW - Smoking

KW - Young Adult

U2 - 10.1007/s00296-013-2904-z

DO - 10.1007/s00296-013-2904-z

M3 - Journal article

C2 - 24264011

VL - 34

SP - 373

EP - 380

JO - Rheumatology International

JF - Rheumatology International

SN - 0172-8172

IS - 3

ER -