Cytokine gene variants and venous thrombotic risk in the BRATROS (BRAZILIAN THROMBOSIS STUDY).
BACKGROUND
Venous thrombosis (VT) and inflammation are two closely related entities. In the present investigation we assessed whether there is a relation between genetic modifiers of the inflammatory response and the risk of VT.


METHODS
420 consecutive and unrelated patients with an objective diagnosis of deep VT and 420 matched controls were investigated. The frequencies of the following gene polymorphisms were determined in all subjects: TNF-alpha-308 G/A, LT-alpha+252 A/G, IL-6-174 G/C, IL1-ra 86 bp VNTR, IL-10-1082 A/G and CD-31 125 C/G.


RESULTS
Overall odds ratio (OR) for VT related to TNF-alpha-308 G/A, LT-alpha+252 A/G, IL-6-174 G/C, A1 allele (4 bp repeat) of the IL1-ra 86 bp VNTR, IL-10-1082 A/G and CD-31 125 C/G were respectively: 1.0 (CI95: 0.8-1.5), 1.3 (CI95: 1.0-1.7), 1.1 (CI95: 0.9-1.5), 1.6 (CI95: 1-2.5), 1.2 (CI95: 0.8-1.7) and 0.8 (CI95: 0.6-1.1). A possible interaction between polymorphisms was observed only for the co-inheritance of the mutant alleles of the LT-alpha+252 A/G and IL-10-1082 G/A polymorphisms (OR=2; CI95: 1.1-3.8). The risk of VT conferred by factor V Leiden and FII G20210A was not substantially altered by co-inheritance with any of the cytokine gene polymorphisms.


CONCLUSIONS
Cytokine gene polymorphisms here investigated did not significantly influence venous thrombotic risk.
Pieroni
Fabiano
F
School of Medicine of Ribeirão Preto, University of São Paulo (USP), Brazil.
Lourenço
Dayse M
DM
Morelli
Vânia M
VM
Maffei
Francisco H
FH
Zago
Marco A
MA
Franco
Rendrik F
RF
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D001938:Brazil; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008233:Lymphotoxin-alpha / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D020246:Venous Thrombosis / Q000209:etiology / Q000235:genetics* / Q000276:immunology*
D016207:Cytokines; D017931:DNA Primers; C508609:IL10 protein, human; C508600:IL6 protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D008233:Lymphotoxin-alpha; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10