Synergistic effect of ALOX5AP polymorphisms and cigarette smoking on the risk of atherosclerotic cerebral infarction in a Northern Han Chinese population

The effect of activating 5-lipoxygenase (ALOX5AP) gene polymorphisms on stroke risk may be influenced by the coexistence of modifiable predisposing conditions. We explored the interactions of ALOX5AP polymorphisms and cigarette smoking in a case-control study of patients with atherosclerotic cerebral infarction (ACI). Three polymorphisms of the ALOX5AP gene (rs10507391, rs4769874, and rs9551963) were analyzed in 420 ACI patients and 488 unrelated healthy controls matched for age and sex from a Northern Han Chinese population. Among the three single nucleotide polymorphisms, only rs10507391 genotype TT/TA was observed to be associated with an increased risk of ACI on multivariate analysis (odds ratio [OR] = 1.82, 95% confidence interval [CI] = 1.14–2.92, p = 0.012) compared with the AA genotype. However, after stratifying by smoking status, multivariate logistic regression analysis revealed that rs10507391 genotype TT/TA and rs9551963 genotype CC/CA had a 5.63-fold (OR = 5.63, 95%CI = 2.00–15.84, p = 0.001) and a 2.71-fold (OR = 2.71, 95%CI = 1.28–5.73, p = 0.009) increased risk for ACI patients who smoked compared with the AA genotype, respectively. Additionally, according to the haplotype analysis, the risk of haplotype TGC (OR = 3.12, 95%CI = 2.00–4.88, p < 0.001, corrected p [pc] < 0.001) increased for ACI patients who smoked compared to the data (OR = 1.60, 95%CI = 1.28–1.98, p < 0.001, pc < 0.001) in total samples. These results suggest that ALOX5AP polymorphisms are associated with ACI, and cigarette smoking along with ALOX5AP could increase the risk of ACI.