Association between tumor necrosis factor-alpha (-308G→A and -238G→A) polymorphisms and homocysteine levels in patients with ischemic strokes and silent brain infarctions.
OBJECTIVE
The aims of this study were to evaluate the role of tumor necrosis factor-α (TNF-α) polymorphisms in patients susceptible to ischemic stroke and silent brain infarction (SBI), and to determine the relationship between TNF-α polymorphisms and plasma total homocysteine (tHcy) levels.


METHODS
We studied 237 patients with ischemic stroke, 257 patients with SBIs, and 216 control subjects. For control subjects, we selected healthy individuals matched for gender and age from those individuals who came to our hospital for health examinations. The TNF-α-308G→A and -238G→A genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism method.


RESULTS
The frequency of the TNF-α-308G→A polymorphism was significantly different between the patients with ischemic stroke and the control group (GG vs. GA+AA; adjusted odds ratio, AOR, 0.50; 95% CI 0.255-0.989). By subgroup analysis, when tHcy levels were stratified into high (>10.80 μmol/l), moderate (8.21-10.80 μmol/l), and low levels (<8.21 μmol/l), the frequency of the TNF-α-308GA+AA genotype in the highest tertile group was higher than in the lowest tertile group (AOR 2.46; 95% CI 1.063-5.699). However, the relationship between SBI susceptibility and polymorphisms of TNF-α was not established. The tHcy levels were significantly and inversely correlated with folate levels in the TNF-α-308GG and TNF-α-238GG genotypes in the ischemic stroke, SBI, and control groups (p< 0.05).


CONCLUSIONS
Our results suggest that the TNF-α-308G→A polymorphism is responsible for susceptibility to ischemic stroke and is associated with high tHcy levels in Koreans.
Kim
Ok Joon
OJ
Institute for Clinical Research, School of Medicine, CHA University, Seongnam, South Korea.
Lee
Jae Ho
JH
Choi
Jeong Kwon
JK
Oh
Seung Hun
SH
Hong
Seung Ho
SH
Oh
Doyeun
D
Kim
Nam Keun
NK
D000368:Aged; D000483:Alleles; D020520:Brain Infarction / Q000097:blood* / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012727:Sex Characteristics; D020521:Stroke / Q000097:blood* / Q000208:ethnology / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha; D006710:Homocysteine