CD40基因rs3765459位点单核苷酸多态性与脑梗死易感性的相关性

目的研究CD40基因rs3765459位点单核苷酸多态性（SNP）与脑梗死易感性之间的关系。 方法选取2015年2月至2017年1月就诊于山西医科大学第二医院的201例脑梗死患者作为病例组，以同一时期就诊于该院体检中心的139名健康人群作为对照组。采用常规酚/氯仿提取法提取外周血白细胞基因组DNA，运用实时荧光定量PCR-TaqMan探针技术检测各样本rs3765459 G/A多态性，进行基因分型。采用t检验比较病例组和对照组年龄间的差异；采用χ²检验比较病例组和对照组间性别、吸烟史、饮酒史、糖尿病史、高脂血症、不同基因型（GG/AG/AA）及等位基因（A/G）的差异，并以OR（95%CI）值表示等位基因（A/G）的相对风险。进一步进行分层分析，比较不同类型脑梗死患者与对照组之间、不同组别相同性别之间以及不同年龄组之间基因型及等位基因的差异。 结果病例组及对照组患者在年龄［（64.12±12.65）岁vs（56.69±11.82）岁］、男性例数（129例vs 73例）方面比较，差异具有统计学意义（t=-71.33，P<0.001；χ²=4.634，P=0.031）。病例组CD40基因rs3765459 A/G位点AA、AG、GG基因型频率分别为11.90%（24/201）、37.80%（76/201）、50.20%（101/201），对照组分别为15.10%（21/139）、49.60%（69/139）和35.30%（49/139），病例组GG基因型及G等位基因频率明显高于对照组，差异具有统计学意义（χ²=7.508，P=0.023），G等位基因携带者患脑梗死的风险增加（OR=1.490，95% CI：1.082~2.052）。分层分析后发现，男性受试者中，病例组GG基因型及G等位基因频率（51.90%，70.80%）明显高于对照组（34.2%，43.2%）；动脉粥样硬化性脑梗死患者GG基因型及G等位基因频率（51.80%，70.20%）明显高于对照组（35.30%，60.10%），且差异均具有统计学意义（P<0.05）。 结论CD40基因rs3765459位点SNP与脑梗死易感性相关，其中G等位基因可能为脑梗死的遗传易感基因，同时该位点基因型分布与卒中亚型（动脉粥样硬化型脑梗死）及性别（男性）相关。

Association of rs3765459 single nucleotide polymorphism of the CD40 gene with cerebral infarction susceptibility

ObjectiveTo determine whether the rs3765459 polymorphism of the CD40 gene is associated with cerebral infarction susceptibility. MethodsTwo hundred and one cerebral infarction patients who were hospitalized at the Second Hospital of Shanxi Medical University from February 2015 to January 2017 were selected as a case group. A group of 139 healthy people who were hospitalized during the same period were selected as a control group. Genomic DNA samples were extracted from the whole blood using the standard phenol/chloroform protocol. The rs3765459 locus A/G polymorphism of the CD40 gene was genotyped by real-time quantitative polymerase chain reaction-TaqMan probe method. The t-test was used to compare the difference in age between the two groups. Sex, smoking history, drinking history, diabetes history, hyperlipidemia, different genotypes (GG/AG/AA) and alleles (A/G) were compared between the two groups by the χ² test. The relative risk of allele (A/G) is expressed as the odds ratio (OR) with 95% confidence interval (95%CI). Further stratified analysis was carried out to compare the genotypes and alleles between patients with different types of cerebral infarction and controls, between different sex groups, and between different age groups. ResultsThere were significant differences in age and male cases between the case group and the control group (64.12±12.65) years vs (56.69±11.82) years, t=71.33, P<0.001; 129 vs 73, χ²=4.634, P<0.031). The frequencies of rs3765459 AA, AG, and GG genotypes were 11.90% (24/201), 37.80% (76/201) and 50.20% (101/201) in the case group, respectively, and 15.10% (21/139), 49.60% (69/139) and 35.30% (49/139) in the control group, respectively. The frequency of GG genotype and G allele in the case group was significantly higher than that in the control group (χ²=7.508, P=0.023). The frequency of G allele in the two groups was 69.20% (278/402) and 60.10% (167/278), respectively, and the difference was statistically significant. The risk of cerebral infarction was increased in G allele carriers (OR=1.490, 95%CI: 1.082-2.052). Stratified analysis showed that GG genotype and G allele frequencies (51.90% and 70.80%, respectively) in the case group were significantly higher than those in the control group (34.2% and 43.2%, respectively). The G/G genotype and G allele frequencies (51.80% and 70.20%, respectively) in patients with atherosclerotic cerebral infarction were significantly higher than those in the control group (35.30% and 60.10%, respectively) (P<0.05). ConclusionThe rs3765459 single nucleotide polymorphisms is associated with susceptibility to cerebral infarction, and G allele may be associated with increased risk of cerebral infarction. The genotype distribution of rs3765459 locus is associated with stroke subtype (atherosclerotic cerebral infarction) and gender (male).