Synergistic effect of -174 G/C polymorphism of the interleukin-6 gene promoter and 469 E/K polymorphism of the intercellular adhesion molecule-1 gene in Italian patients with history of ischemic stroke.
OBJECTIVE
Interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) are involved in the pathogenetic mechanisms responsible for several ischemic cardiovascular disorders, including cerebral ischemia. IL-6 and ICAM-1 plasma levels and/or function may be genetically influenced. We sought to evaluate distribution and reciprocal interaction of IL-6 G/C gene promoter polymorphism and ICAM-1 E/K gene polymorphism in Italian patients with history of ischemic stroke.


METHODS
One hundred nineteen patients with history of ischemic stroke and 133 age- and sex-matched controls were studied. IL-6 and ICAM-1 genotypes were evaluated by polymerase chain reaction and restriction enzyme analysis.


RESULTS
The GG genotype of -174 IL-6 G/C gene polymorphism was significantly associated with history of ischemic stroke at both univariate (P<0.0001) and multivariate analysis (odds ratio [OR], 8.6; P<0.0001). Additionally, the EE genotype of ICAM-1 E/K gene polymorphism was significantly more common in the group of patients with history of ischemic stroke (P=0.003) and was an independent variable associated with stroke history (OR, 4.0; P=0.002). Interestingly, a further increased risk of stroke was found in subjects who concomitantly carry the IL-6 GG and ICAM-1 EE genotypes (IL-6 GG/ICAM-1 EE double-homozygous subjects) (OR, 10.1; P=0.004).


CONCLUSIONS
There is a synergistic effect of IL-6 G/C and ICAM-1 E/K gene polymorphisms in patients with stroke history. Reciprocal interactions between genotypes may contribute in determining the risk profile for cardiovascular diseases and may merit further investigation as potential therapeutic targets.
Pola
Roberto
R
Laboratory of Vascular Biology and Genetics, Department of Geriatric Medicine, A. Gemelli University Hospital, Università Cattolica del Sacro Cuore School of Medicine, Rome, Italy. rob_pola@hotmail.com
Flex
Andrea
A
Gaetani
Eleonora
E
Flore
Roberto
R
Serricchio
Michele
M
Pola
Paolo
P
D000368:Aged; D019943:Amino Acid Substitution; D002545:Brain Ischemia / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D007558:Italy; D008297:Male; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D020521:Stroke / Q000175:diagnosis / Q000235:genetics*
D015850:Interleukin-6; D018799:Intercellular Adhesion Molecule-1