中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (11): 1986-1993.doi: 10.4103/1673-5374.259621

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

PPARγ基因多态性与中国北方汉族人群患缺血性脑卒中风险的相关性：病例-对照研究

  

  • 出版日期:2019-11-15 发布日期:2019-11-15
  • 基金资助:

    国家自然科学基金(81070913)

Association between PPARG genetic polymorphisms and ischemic stroke risk in a northern Chinese Han population: a case-control study

Yan-Zhe Wang, He-Yu Zhang, Fang Liu, Lei Li, Shu-Min Deng, Zhi-Yi He   

  1. Department of Neurology, the First Hospital of China Medical University, Shenyang, Liaoning Province, China
  • Online:2019-11-15 Published:2019-11-15
  • Contact: Zhi-Yi He, MD, PhD, hezhiyi0301@sina.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81070913 (to ZYH).

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摘要：

研究表明，过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptor gamma，PPARγ)基因上的单核苷酸多态性(single nucleotide polymorphism，SNP)rs1801282及rs3856806可能是影响缺血性脑卒中易感性的重要候选基因位点。试验拟采用病例-对照研究方法探讨PPARγ基因多态性和中国人群缺血性脑卒中的相关性。收集中国医科大学附属第一医院神经内科住院的缺血性脑卒中患者895例以及该医院体检中心的健康体检者883例，均属中国北方汉族人群，分别设为病例组和对照组。提取两组参与者血浆基因组DNA，利用SNaPshot技术进行PPARγ基因多态性位点(rs1801282及rs3856806)分型。结果发现，PPARγ基因rs1801282位点的G等位基因频率在病例组明显高于对照组(P < 0.001)。携带G等位基因的个体发生缺血性脑卒中的危险增加到1.844倍(OR = 1.844，95%CI：1.286-2.645；P < 0.001)。携带rs3856806位点T等位基因的个体发生缺血性脑卒中的危险度增加到1.366倍(OR = 1.366，95%CI：1.077-1.733；P = 0.010)。PPARγ基因单倍型rs1801282-rs3856806的单倍型在对照组与病例组中的分布频率：G-T单倍型缺血性脑卒中组中的分布频率明显高于对照组，携带G-T单倍型的个体，患缺血性脑卒中的风险率增加至2.953倍(OR = 2.953；95%CI：2.082-4.190；P < 0.001)。PPARγ基因rs1801282的G等位基因及rs3856806的T等位基因对缺血性脑卒中存在相乘交互作用(OR = 3.404；95%CI：1.631-7.102；P < 0.001)及相加交互作用(RERI = 41.705；95%CI：14.586-68.824；AP= 0.860；95%CI：0.779-0.940；S= 8.170；95%CI：3.772-17.697)，此时为协同作用。全部缺血性脑卒中病例中归因于rs1801282的G等位基因及rs3856806的T等位基因交互作用引起的病例占86%。PPARγ基因rs1801282的G等位基因对缺血性脑卒中的影响作用在rs3856806的T等位基因存在下有所增强(OR=8.001 vs. 1.844)，rs3856806的T等位基因的对缺血性脑卒中的影响作用在rs1801282的G等位基因存在下也有所增强(OR = 2.546 vs. 1.366)。结果证实，PPARγ基因rs1801282的G等位基因及rs3856806的T等位基因可能是中国北方汉族人群患缺血性脑卒中的独立危险因素，并且此2等位基因间存在协同作用。所有参与者或家属均签署知情同意书，研究已经过中国医科大学第一附属医院医学伦理委员会批准，批准号：2012-38-1，批准时间2012-02-20。研究已在中国临床试验注册中心注册，注册号：ChiCTR-COC-17013559，注册时间：2017-11-27。

orcid: 0000-0002-0995-0294(Zhi-Yi He)

关键词: 神经再生, 卒中, 脑缺血, 缺血性脑卒中, 过氧化物酶体增殖物激活受体γ, 单核苷酸多态性, 单倍型分析, 交互作用, 病例-对照研究, 中国北方汉族人群

Abstract:

Two common polymorphisms of the peroxisome proliferator-activated receptor gamma (PPARG) gene, rs1801282 and rs3856806, may be important candidate gene loci affecting the susceptibility to ischemic stroke. This case-control study sought to identify the relationship between these two single-nucleotide polymorphisms and ischemic stroke risk in a northern Chinese Han population. A total of 910 ischemic stroke participants were recruited from the First Hospital of China Medical University, Shenyang, China as a case group, of whom 895 completed the study. The 883 healthy controls were recruited from the Health Check Center of the First Hospital of China Medical University, Shenyang, China. All participants or family members provided informed consent. The study protocol was approved by the Ethics
Committee of the First Hospital of China Medical University, China on February 20, 2012 (approval No. 2012-38-1). The protocol was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR-COC-17013559). Plasma genomic DNA was extracted from all participants and analyzed for rs1801282 and rs3856806 single nucleotide polymorphisms using a SNaPshot Multiplex sequencing assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression to estimate the association between ischemic stroke and a particular genotype. Results demonstrated that the G allele frequency of the PPARG gene rs1801282 locus was significantly higher in the case group than in the control group (P < 0.001). Individuals carrying the G allele had a 1.844 fold increased risk of ischemic stroke (OR = 1.844, 95% CI: 1.286–2.645, P < 0.001). Individuals carrying the rs3856806 T allele had a 1.366 fold increased risk of ischemic stroke (OR = 1.366, 95% CI: 1.077–1.733, P = 0.010). The distribution frequencies of the PPARG gene haplotypes rs1801282-rs3856806 in the control and case groups were determined. The frequency of distribution in the G-T haplotype case group was significantly higher than that in the control group. The risk of ischemic stroke increased to 2.953 times in individuals carrying the G-T haplotype (OR = 2.953, 95% CI: 2.082–4.190, P < 0.001). The rs1801282 G allele and rs3856806 T allele had a multiplicative interaction (OR = 3.404, 95% CI: 1.631–7.102, P < 0.001) and additive interaction (RERI = 41.705, 95% CI: 14.586–68.824, AP = 0.860; 95% CI: 0.779–0.940; S = 8.170, 95% CI: 3.772–17.697) on ischemic stroke risk, showing a synergistic effect. Of all ischemic stroke cases, 86% were attributed to the interaction of the G allele of rs1801282 and the T allele of rs3856806. The effect of the PPARG rs1801282 G allele on ischemic stroke risk was enhanced in the presence of the rs3856806 T allele (OR = 8.001 vs. 1.844). The effect of the rs3856806 T allele on ischemic stroke risk was also enhanced in the presence of the rs1801282 G allele (OR = 2.546 vs. 1.366). Our results confirmed that the G allele of the PPARG gene rs1801282 locus and the T allele of the rs3856806 locus may be independent risk factors for ischemic stroke in the Han population of northern China, with a synergistic effect between the two alleles.

Key words: nerve regeneration, stroke, cerebral ischemia, ischemic stroke, peroxisome proliferator-activated receptor γ, single-nucleotide polymorphism, haplotype analysis, interaction, case-control study, Chinese Han population, neural regeneration