Hua Liu1,2,3, Danyang Luo1,2, Ya Qiu4, Yan Huang3, Cheng Chen5, Xiaoxiao Song6, Li Gao1, Yongmei Zhou1. 1. 1 Department of Neurology, the Third People's Hospital of Chengdu, the Affiliated Hospital of Southwest Jiaotong University, Chengdu, P.R. China. 2. 2 Department of Neurology, Nanchong Central Hospital, Southwest Medical University, Nanchong, P.R. China. 3. 3 Department of Neurology, Yanting County People's Hospital, Yanting, P.R. China. 4. 4 Institute of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, Nanchong, P.R. China. 5. 5 Department of Neurology, Chengdu Hospital of the Chinese People's Armed Police Forces, Chengdu, P.R. China. 6. 6 Department of Epidemiology and Statistics, School of Public Health, Kunming Medical University, Kunming, P.R. China.
Abstract
Background/ Objectives: Ischemic stroke (IS) is a severe and complex disorder with high morbidity and mortality rates and it has been associated with both environmental and genetic predisposing factors. The purpose of this study was to evaluate the association of the alpha-1-microglobulin/bikunin precursor (AMBP) gene polymorphisms with IS and any possible interactions between specific AMBP alleles and traditional risk factors among a Han Chinese cohort. Materials and Methods: We conducted a candidate gene study designed to characterize nine (9) single nucleotide polymorphisms (SNPs) of the AMBP gene among 195 patients with atherothrombotic stroke (ATS) (a major subtype of IS) and 184 nonstroke controls. Allelic and genotypic frequency differences were evaluated using a logistic regression model. False discovery rate (FDR) correction for multiple comparisons was used. The interactional analyses were performed using the multifactor dimensionality reduction test. Results: We found an association between the rs2567698 CC genotype (odds ratio [OR], 95% confidence interval [CI]: 2.176, 1.159-4.086) and the T allele (OR, 95% CI: 0.654, 0.446-0.960) with risk of ATS in men. However, these associations did not survive FDR correction. In haplotype analyses, the GCCCCCCCC haplotype had a higher frequency (OR, 95% CI: 2.191, 1.048-4.580) in ATS in the ≥45 years of age subgroup, whereas the GCCTCCCCC haplotype decreased the risk for ATS (OR, 95% CI: 0.543, 0.345-0.853) in men. In addition, we also found interactions for ATS risk between SNPs in the AMBP gene and modifiable risk factors for ATS, including: rs11788411 and hypertension in the overall population and women; rs2251680 and hypertension in subjects aged 45 years and older, as well as the interaction among hypertension and the rs2567698 and rs10817564 genotypes in men. Conclusion: Our results show a possible association between AMBP SNP haplotypes and gene-environment interactions with ATS susceptibility in a Han Chinese cohort.
Background/ Objectives:Ischemic stroke (IS) is a severe and complex disorder with high morbidity and mortality rates and it has been associated with both environmental and genetic predisposing factors. The purpose of this study was to evaluate the association of the alpha-1-microglobulin/bikunin precursor (AMBP) gene polymorphisms with IS and any possible interactions between specific AMBP alleles and traditional risk factors among a Han Chinese cohort. Materials and Methods: We conducted a candidate gene study designed to characterize nine (9) single nucleotide polymorphisms (SNPs) of the AMBP gene among 195 patients with atherothrombotic stroke (ATS) (a major subtype of IS) and 184 nonstroke controls. Allelic and genotypic frequency differences were evaluated using a logistic regression model. False discovery rate (FDR) correction for multiple comparisons was used. The interactional analyses were performed using the multifactor dimensionality reduction test. Results: We found an association between the rs2567698 CC genotype (odds ratio [OR], 95% confidence interval [CI]: 2.176, 1.159-4.086) and the T allele (OR, 95% CI: 0.654, 0.446-0.960) with risk of ATS in men. However, these associations did not survive FDR correction. In haplotype analyses, the GCCCCCCCC haplotype had a higher frequency (OR, 95% CI: 2.191, 1.048-4.580) in ATS in the ≥45 years of age subgroup, whereas the GCCTCCCCC haplotype decreased the risk for ATS (OR, 95% CI: 0.543, 0.345-0.853) in men. In addition, we also found interactions for ATS risk between SNPs in the AMBP gene and modifiable risk factors for ATS, including: rs11788411 and hypertension in the overall population and women; rs2251680 and hypertension in subjects aged 45 years and older, as well as the interaction among hypertension and the rs2567698 and rs10817564 genotypes in men. Conclusion: Our results show a possible association between AMBP SNP haplotypes and gene-environment interactions with ATS susceptibility in a Han Chinese cohort.