Tumor necrosis factor-alpha -1031 T/C polymorphism is associated with smaller and more proatherogenic low density lipoprotein particles in patients with rheumatoid arthritis.
OBJECTIVE
To study, in patients with rheumatoid arthritis (RA), the association between the tumor necrosis factor (TNF)-alpha -1031 T/C polymorphism and quantitative and qualitative low density lipoprotein (LDL) characteristics.


METHODS
From a sample of 100 patients with RA and 100 controls, we used the strategy of "recruit by genotype" to select 30 patients with RA: 15 carriers of the rare allele (C) and 15 homozygous for the more frequent allele (T). These were matched with 30 controls. Plasma lipoprotein profile including size distribution of lipoproteins was determined using nuclear magnetic resonance spectrometry. LDL susceptibility to oxidation was assessed by diene formation. The LDL affinity for extracellular matrix was determined using electrophoretic mobility shift assay. Genotyping was performed by SnapShot.


RESULTS
Compared to TT patients with RA, carriers of the C allele had (1) LDL particles significantly smaller [20.74 (0.68) nm vs 21.18 (0.52), p < 0.02]; (2) LDL particles with a greater affinity for the proteoglycans (i.e., with a lower Kd) [197.26 (123.98) nmol/l vs 259.26 (139.31), p = 0.05]; and (3) LDL particles with significantly greater susceptibility to oxidation [shorter lag phase: 47 (20.01) min vs 74 (41.8), p < 0.03, and higher maximal rate of diene production: 3.1 (0.5) mol/min vs 2.6 (0.95), p < 0.05]. None of these differences was observed in the control group.


CONCLUSIONS
In patients with RA, genetic variability in the TNF-alpha gene is associated with smaller LDL particles that have a greater affinity for extracellular matrix and higher susceptibility to oxidation. Because these characteristics are associated with a greater risk of atherosclerosis, identification of such predisposition in patients with RA could help in implementing early preventive intervention measures against cardiovascular disease.
Vallvé
Joan-Carles
JC
From Unitat de Recerca de Lípids i Arteriosclerosi, Facultat de Medicina, Universitat Rovira i Virgili, Reus, Catalonia, Spain; and Cell Biology and Biochemistry, AstraZeneca, Lund, Sweden.
Paredes
Silvia
S
Girona
Josefa
J
Uliaque
Katia
K
Ribalta
Josep
J
Hurt-Camejo
Eva
E
Masana
Lluís
L
D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*
D008077:Lipoproteins, LDL; D014409:Tumor Necrosis Factor-alpha