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生物钟核心基因多态性与缺血性脑卒中疾病的关联性

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目的 探索生物钟分子发条中核心时钟基因单核苷酸多态性ARNTL rs6486122、PER1 rs2253820与缺血性卒中发病的关联性。方法 采用SNaPshot法检测候选SNPs基因型。不同的基因型被当作分类变量,疾病组与对照组间基因型及遗传模型的比较采用Logistic回归分析,并校正年龄、性别、血脂异常、既往病史等相关危险因素,分别计算不同基因型及遗传模型的调整OR值和95%CI。结果 多因素Logistic回归分析显示,随着受试者年龄的增长脑卒中的患病风险显著增加(P<0。001,OR=6。704,95%CI 5。188~8。644);高血压患者较非高血压患者的患缺血性脑卒中风险增加2。565倍(P<0。001,OR=2。565,95%CI 1。971~3。338);血脂异常患者较血脂正常人群患缺血性脑卒中的风险增加1。700倍(P=0。001,OR=1。700,95%CI 1。230~2。348);收缩压及舒张压增高,同样也会增加卒中的患病风险。对于PER1基因rs2253820位点,以野生纯合子TT基因型为参比,CT基因型,CC基因型以及显性遗传模型在增加脑卒中的发病风险方面均具有统计学意义(CT vs TT:P=0。001,OR=1。552,95%CI 1。194~2。018;CC vs TT:P=0。024,OR=1。295,95%CI 1。035~1。621;显性模型:P=0。001,OR=1。563,95%CI 1。215~2。012。对于ARNTL基因的rs 6486122位点,经校正后,各基因型与遗传模型与缺血性脑卒中发病的关联性无统计学意义(P>0。05)。结论 PER1 rs2253820位点的遗传变异会增加缺血性卒中的患病风险,PER1 rs2253820位点携带C等位基因患缺血性卒中的危险更高。ARNTL rs6486122位点与缺血性脑卒中发病关联性无统计学意义。
Association of core circadian clock gene polymorphism with ischemic stroke
Objective To explore the association between the single nucleotide polymorphism(SNP)of the core clock genes(ARNTL rs6486122 and PER1 rs2253820)of the circadian molecular clockwork and the incidence of ischemic stroke.Methods Candidate SNP genotypes were determined using the SNaPshot method.Genotypes were set as categorical vari-ables.Logistic regression analysis was performed to compare genotypes and genetic models between the disease group and the control group,adjusting for related risk factors including age,sex,dyslipidemia,and past medical history,and the adjusted odds ratios(OR)and 95%confidence intervals(CI)of different genotypes and genetic models were calculated.Results The multivariable logistic regression analysis showed that the risk of stroke increased significantly with the age of subjects(OR= 6.704,95%CI 5.188-8.644,P<0.001);patients with hypertension had a 2.565-fold increased risk of ischemic stroke com-pared with individuals without hypertension(OR=2.565,95%CI 1.971-3.338,P<0.001);patients with dyslipidemia were 1.700 times more likely to have ischemic stroke than individuals with normal blood lipid levels(OR=1.700,95%CI 1.230-2.348,P=0.001);and increased systolic and diastolic blood pressure levels also increased the risk of stroke.For the rs2253820 locus of the PER1 gene,using the wild-type homozygous TT genotype as the reference,the CT genotype,CC geno-type,and dominant genetic model significantly increased the risk of stroke(CT vs TT:OR=1.552,95%CI 1.194-2.018,P= 0.001;CC vs TT:OR=1.295,95%CI 1.035-1.621,P=0.024;and the dominant model:OR=1.563,95%CI 1.215-2.012,P=0.001,respectively).For the rs6486122 locus of the ARNTL gene,there was no significant association of any geno-type or the genetic model with the incidence of ischemic stroke after adjustment(P>0.05).Conclusion Genetic variation at PER1 rs2253820 can increase the risk of ischemic stroke,where the C allele poses a higher risk of ischemic stroke.There is no significant association between ARNTL rs6486122 and the occurrence of ischemic stroke.

Circadian clock geneSingle nucleotide polymorphismIschemic stroke

施海媛、谭沙一君、李路明、刘如、刘逊、何明利

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南京医科大学连云港临床医学院,江苏 连云港 222002

徐州医科大学附属连云港医院,江苏 连云港 222002

生物钟基因 单核苷酸多态性 缺血性卒中

国家自然科学基金资助项目

81970348

2024

中风与神经疾病杂志
吉林大学

中风与神经疾病杂志

CSTPCD
影响因子:0.754
ISSN:1003-2754
年,卷(期):2024.41(2)
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