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白细胞分化抗原-40基因SNP及其血清水平与缺血性脑卒中的相关性
作者:陈健明 黄华佗 袁秋然 罗宏成 向阳 王春芳 蒙兰青 韦叶生

摘要:

目的  研究白细胞分化抗原-40(CD40)基因SNP及其血清水平与缺血性脑卒中(IS)易感性之间的关系。方法  选择2013年5月至2014年11月就诊于百色市某医院的缺血性脑卒中患者作为病例组,共202例。以同一时期在该医院门诊部进行体检的109名健康人群作为对照组。所有调查对象均来自广西壮族自治区,且相互间无血缘关系。经知情同意,每名调查对象均采集空腹静脉血3 ml,用单碱基延伸的PCR技术对CD40基因rs1883832 C/T、rs13040307 C/T、rs752118 C/T和rs3765459 G/A多态性进行基因分型,同时采用ELISA检测血清CD40水平。采用t检验比较CD40血清水平在病例组与对照组间的差异及病例组中各位点不同基因型间的差异;采用χ2检验比较CD40基因不同位点基因型及等位基因在病例组和对照组中的分布差异,并以OR(95%CI)值表示相对风险。结果  病例组CD40基因rs1883832 C/T位点CC、CT、TT基因型频率分别为21.78%(44/202)、49.51%(100/202)、28.71%(58/202),对照组分别为33.17%(66/199)、48.74%(97/199)和18.09%(36/199),两组差异有统计学意义(χ2=9.57,P=0.008)。病例组CD40血清水平为(62.7±24.5) pg/ml,高于对照组[(45.3±17.2) pg/ml](t=8.97,P<0.001);病例组中rs1883832 C/T位点TT、CT基因型CD40血清水平分别为(65.9±26.3)、(64.3 ± 25.9)pg/ml,均高于CC基因型CD40血清水平[(55.1 ± 23.7)pg/ml](t值分别为5.34和5.03,P值均<0.001)。与rs1883832 C/T位点C等位基因携带者相比,T等位基因携带者患缺血性脑卒中的风险增加(OR=1.56, 95% CI:1.18~2.06)。联合基因型分析后发现,与对照组比较,病例组TCCA单倍型的携带者增加了缺血性脑卒中的发病风险(OR=2.49,95% CI:1.13~5.48)。结论  CD40基因rs1883832 C/T位点和TCCA单倍型与缺血性脑卒中的发病可能存在相关性,其中缺血性脑卒中的遗传易感基因可能是T等位基因。

关键词:抗原,CD;多态性,单核苷酸;病例对照研究;基因;缺血性脑卒中

Abstract:

Objective  To investigate the association of SNP of CD40 gene and its serum levels with ischemic stroke (IS).Methods  A total of 202 IS patients from a hospital of Baise city were enrolled in case group from May 2013 to November 2014. At the same time, 109 healthy people who had physical check-ups in the outpatient department at the same hospital were enrolled in the control group. All participants were from Guangxi Zhuang Autonomous Region and unrelated to each other. 3 ml venous blood were collected on the premise of informed consent. The single nucleotide polymorphisms of CD40 gene rs1883832 C/T, rs13040307 C/T, rs752118 C/T and rs3765459 G/A were analyzed using a Snapshot SNP genotyping assays, and the serum levels of CD40 were tested by ELISA. t-test was used to compare the serum levels of CD40 between the case and control group, and the genotypes at different locuses in case group; χ2 test was used to compare the distribution differences of the CD40 gene locuses in different genotypes and allele between the case group and the control group; alleles was established as independent variables, the occurrence of the IS as dependent variable, and expressed relative risk with OR (95%CI) value.Results  In the case group, the frequency of CC, CT and TT genotypes in CD40 gene rs1883832 C/T were 21.78% (44/202), 49.51% (100/202) and 28.71% (58/202), respectively, and 33.17% (66/199), 48.74% (97/199), 18.09% (36/199) in the control group, respectively, the differences between the two groups was significant (χ2=9.57, P=0.008). The CD40 serum levels were (62.7±24.5) pg/ml in the case group, which was higher than that in the control group (45.3±17.2) pg/ml (t=8.97, P<0.001). The serum levels of TT and CT genotypes in CD40 gene were (65.9±26.3) and (64.3±25.9) pg/ml, respectively, and the differences were significant when comparing with CC genotype (t equaled 5.34 and 5.03, respectively, P<0.001). The risk of developing IS was 1.56 times higher in 1883832 T allele carriers than that in rs1883832 C allele carriers (OR=1.56, 95% CI: 1.18-2.06); Combined genotype analysis displayed that CD40 gene rs1883832 C/T, rs13040307 C/T, rs752118 C/T and rs3765459 G/A polymorphisms showed strong linkage disequilibrium, the case group TCCA haplotype was tested to be associated with a significantly increased risk of IS as compared with that in the control group(OR=2.49; 95%CI: 1.13-5.48).Conclusion  CD40 gene rs1883832 C/T polymorphism and its TCCA haplotype were possibly associated with ischemic stroke, and the susceptibility gene for ischemic stroke may be rs1883832 T allele.

Key words: Antigens, CD;Polymorphism, single nucleotide;Case-control study;Gene;Ischemic stroke

发表日期:2016/3

引用本文:

图/表:

  • 10.3760/cma.j.issn.0253-9624.2016.03.010.T001

    10.3760/cma.j.issn.0253-9624.2016.03.010.T001

  • 10.3760/cma.j.issn.0253-9624.2016.03.010.T002:表2 对照组和病例组CD40基因各位点分布差异比较[n(%)]

    10.3760/cma.j.issn.0253-9624.2016.03.010.T002:表2 对照组和病例组CD40基因各位点分布差异比较[n(%)]

  • 10.3760/cma.j.issn.0253-9624.2016.03.010.T003:表3 对照组和病例组CD40基因各位点等位基因的分布差异比较及其与缺血性脑卒中发病风险的关系

    10.3760/cma.j.issn.0253-9624.2016.03.010.T003:表3 对照组和病例组CD40基因各位点等位基因的分布差异比较及其与缺血性脑卒中发病风险的关系

  • 10.3760/cma.j.issn.0253-9624.2016.03.010.T004:表4 对照组和病例组CD40基因单倍型的分布差异比较及其与缺血性脑卒中发病风险的关系

    10.3760/cma.j.issn.0253-9624.2016.03.010.T004:表4 对照组和病例组CD40基因单倍型的分布差异比较及其与缺血性脑卒中发病风险的关系

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