| BackgroundThe incidence of stroke has increased markedly to become the second cause of death and disability in China. Stroke is a polygenic disease resulted by genetic factors and environment factors. Recent studies found genetic factors is important in the mechanism of ischemic stroke.Adiponectin is the most abundant adipokine secreted by the adipose tissue, and it plays an important role in the regulation of energy homeostasis, glucose and lipid metabolisms. Inflammation-related atherosclerosis is the leading important cause of ischemic stroke. Adiponectin has protective actions in the initiation and progression of atherosclerosis through anti-inflammatory and anti-atherogenic effects. Adiponectin is inversely associated with the risk of ischemic stroke through its anti-inflammatory and anti-atherogenic effects. Clinical studies have also shown the level of plasma adiponectin is decreased in the patients with ischemic stroke. Moreover, low level of plasma adiponectin is independently associated with the increased risk of mortality after ischemic stroke. Genetic variations in the adiponectin gene (ADIPOQ) have been shown to be associated with the risk of ischemic stroke in Caucasians and Japanese populations. However, it was unknown whether variations in the ADIPOQ gene and the adiponectin receptor genes were associated with the risk of ischemic stroke in Chinese population.MethodsThis study population consisted of 302 patients with ischemic stroke and 338 healthy controls. All the subjects were unrelated Chinese Han population in northern China. The patients were consecutively hospitalized in Department of Neurology, the First Affiliated Hospital and the Shengjing Hospital of China Medical University from September 2008 to May 2009. The controls were recruited from the health examination department of the First Affiliated Hospital of China Medical University, matched by sex and age. The single-nucleotide polymorphisms (SNPs) rs266729 (-11377C/G), rs2241766 (+45T/G), rs1501299 (+276G/T) in the ADIPOQ gene, rs1342387(+5843G/A) in the adiponectin receptor 1 gene and rs12342 (+33371G/A) in the adiponectin receptor 2 gene were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.ResultsThe frequencies of GG genotype and G allele of rs266729 in the patients with ischemic stroke were significantly higher than those in the controls (p=0.034, p= 0.010, respectively). In univariate logistic analysis, compared with CC genotype, GG genotype of rs266729 increased the risk of ischemic stroke (odds ratio (OR)=2.062, 95% confidence interval (CI)=1.145～3.715, p=0.016). After adjustment for potential risk factors by the multivariate logistic analysis, rs266729 remained positive correlation with ischemic stroke (OR=2.165;95% CI=1.116～4.197,p=0.022). The frequencies of AA genotype and A allele of rs12342 in the patients with ischemic stroke were significantly higher than those in the controls (P=0.011 and P=0.002 respectively). In univariate logistic analysis, compared with CC genotype, GG genotype of rs12342 increased the risk of ischemic stroke (OR=1.874,95% CI= 1.221～2.876, p=0.004). After adjustment for potential risk factors by the multivariate logistic analysis, rs12342 remained positive correlation with ischemic stroke (OR= 1.802; 95% CI=1.108～2.933, p=0.018). However, no significant association was observed among rs2241766, rs1501299, ts1342387 and ischemic stroke. In addition, our results showed that pair-wise LDs of rs266729, rs2241766 and rs 1501299 were weak using the SHEsis software. In the haplotype analysis, five major haplotypes with frequencies more than 5% were identified, accounting for 87% of total haplotypes; however, no significant difference was observed in haplotype frequencies between ischemic stroke patients and controls.ConclusionsThe present study demonstrated that the promoter polymorphism rs266729 of the ADIPOQ gene and the rs12342 of the ADIPOR2 gene were associated with an increased risk of ischemic stroke in the Chinese Han population. The SNPs rs2241766 and rs1501299 of the ADIPOQ gene and rs1342387 of the ADIPOR1 gene were not associated with the risk of ischemic stroke in the Chinese population. no significant difference was observed in haplotype frequencies between ischemic stroke patients and controls. The pair-wise LDs of rs266729, rs2241766 and rs 1501299 were weak.
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