Secreted frizzled-related protein 1 gene polymorphisms and smoking in large artery atherosclerotic stroke

Objective To investigate the impact of secreted frizzled-related protein 1 (SFRP 1) gene polymorphisms and gene-smoking interactions on the risk of large artery atherosclerotic (LAA) stroke. Methods Two hundred and sixty-four patients diagnosed with LAA stroke and 228 healthy controls were enrolled from the Department of Neurology, Affiliated Hospital of Qingdao University from August 2016 to June 2017. The methods of polymerase chain reaction-restriction fragment length polymorphism, combined with DNA sequencing, were used to detect the three single nucleotide polymorphisms (SNPs: rs7832767, rs1127379, rs3242) in the SFRP 1 gene. Logistic regression was applied to analyze associations between SNPs and LAA stroke. Cross analysis of additive model was used to evaluate gene-smoking interactions. Results The genotype TT/CT and allele T of rs7832767 in case group were in higher frequency than that in controls (54.9% (145/264) vs 37.7% (86/228), OR=2.123, 95% CI 1.482-3.041, P<0.01; 33.9% (179/528)vs 20.0%(91/456), OR=2.057, 95% CI 1.536-2.755, P<0.01). However, the frequencies of genotypes and alleles in other SNPs (rs1127379, rs3242) showed no significant differences between cases and controls. Multivariate Logistic regression analysis showed that TT/CT genotype was a risk factor for LAA stroke (OR=1.649, 95% CI 1.066-2.550, P=0.025). Moreover, SFRP 1 gene was not related to the distribution of cerebralvascular stenosis in LAA stroke patients. Additive model analysis showed significant interactions between rs7832767 and smoking (relative excess risk of interaction=2.442, 95% CI 0.281-4.603). Smokers with T allele of rs7832767 showed significantly increased risk of LAA stroke (OR=3.252, 95% CI 1.629-6.491, P=0.001). Whereas, no significant interaction was detected between rs3242 or rs1127379 and smoking. Conclusion The T allele of rs7832767 within SFRP 1 gene may be a risk factor of LAA stroke, and the interactions between rs7832767 and smoking can significantly increase the risk of LAA stroke. Key words: Stroke; Smoking; Atherosclerosis; Polymorphism, single nucleotide