ANRIL,PON基因及其交互效应对急性缺血性脑卒中后认知损伤的影响

The effect of ANRIL,PON gene and their interactions on cognitive impairment in acute ischemic stroke patients

目的探讨ANRIL,PON基因及其交互效应对急性缺血性脑卒中(IS)后认知损伤(PSCI)的影响。方法以17~70岁汉族初发急性IS患者作为研究对象,发病后2周采用简易智能量表(MMSE)进行认知测定,检测ANRIL和PON基因单核苷酸多态性(SNPs),采用多因素回归方法和多因子降维法(MDR)分析IS后认知损伤的传统危险因素和易感基因位点以及它们之间的交互作用。结果共纳入研究对象255例,88例具有程度不同的认知损伤(34.5%)。分析发现,rs10116277 G等位基因携带者认知损伤发病风险更小(OR=0.128,P=0.001),rs1333049 C等位基因(OR=1.472,P=0.038)、rs12026(OR=2.595,P=0.015)和rs7493 GG基因型(OR=2.597,P=0.015)、以及rs3735590 A等位基因(OR=1.731,P=0.034)增加了认知损伤发病风险;交互作用分析发现,携带rs10116277 TT基因型和rs1333049 CC基因型的高hsCRP值患者(OR=5.049,P=0.005)、携带rs10116277 TT基因型和rs1333049 CC基因型的大中面积脑梗死患者(OR=8.322,P=0.001)、携带rs10116277 TT基因型的颈动脉中重度狭窄患者(OR=4.067,P=0.001)、以及携带rs3735590 GG基因型的大中面积梗死患者(OR=5.176,P<0.001)认知损伤发生率显著升高。结论ANRIL,PON基因与PSCI发病风险密切相关。

Objective To evaluate the association of the ANRIL and PON gene with cognitive impairment in acute ischemic stroke(PSCI)using single nucleotide polymorphisms(SNPs)as gene marker and any possible interactions between specific genotypes and traditional risk factors for PSCI among a Han Chinese cohort.Methods The samples consisted of the Han people with first-ever ischemic stroke(IS)at the age of ranging from 17 to 70 years.The cognitive function was evaluated at 2 weeks after IS onset according to the Chinese version of Mini-Mental State Examination(MMSE).The SNPs were detected by SNPscan methods based on polymerase chain reaction principle.Allelic and genotypic frequency differences were evaluated using a Logistic regression model.The interactional analyses were performed using the multifactor dimensionality reduction test.Results A total of 255 patients were entered into the study and 88 patients were diagnosed as PSCI(34.5%).We found an association between the rs10116277 G allele(OR=0.128,P=0.001),rs1333049 C allele(OR=1.472,P=0.038),rs12026(OR=2.595,P=0.015)and rs7493 GG genotype(OR=2.597,P=0.015),and rs3735590 A allele(OR=1.731,P=0.034)and PSCI.In addition,we also found interactions for PSCI risk between SNPs in the ANRIL and PON gene and traditional risk factors,including:rs10116277 TT genotype,rs1333049 CC genotype and high levels of hsCRP(OR=5.049,P=0.005);rs10116277 TT genotype,rs1333049 CC genotype and infarction volume(OR=8.322,P=0.001);rs10116277 TT genotype and carotid stenosis(OR=4.067,P=0.001);as well as rs3735590 GG genotype and infarction volume(OR=5.176,P<0.001).Conclusion The ANRIL and PON SNPs as well as the gene-environment interactions play an important role in PSCI in a Han Chinese cohort.