染色体9P21多态性与大动脉粥样硬化型脑梗死的相关性研究

发布时间：2018-07-02 10:21

本文选题：9p21 + 大动脉粥样硬化型脑梗死　；参考：《中南大学》2014年硕士论文

【摘要】：目的：探讨染色体9p21的全基因组关联研究(Genome-wide association study, GWAS)阳性位点rs10757274及染色体9p21的1号单倍型区域位点rs7049105、rs647188、rs1333035与湖南长沙地区汉族人群大动脉粥样硬化型脑梗死(Large-artery atherosclerosis stroke, LAS)的相关性；探讨rs7049105、rs647188、rs1333035位点在有头颈部动脉粥样硬化证据的人群中与LAS的相关性,为LAS的诊断与治疗靶点提供理论依据。方法：采用病例对照研究方法收集湖南长沙地区汉族人群中229例LAS患者为病例组,收集同期门诊及体检中心“健康”人群中233例样本为对照组1,其中有动脉粥样硬化证据的样本150例(64.38%)纳入对照组2,无动脉粥样硬化证据的样本83例(35.62%)纳入对照组3。利用基质辅助激光解析飞行时间质谱(matrix-assisted laser desorption inoization-time of flight mass spectrometry, MALDI-TOF-MS)方法对样本进行基因分型检测,统计分析比较病例组与对照组间rs10757274位点的多态性分布,并采用Meta分析的方法结合本次研究及已发表的rs10757274位点与LAS相关性研究进行定量分析。接着比较病例组与对照组间rs7049105、rs647188、rs1333035位点的多态性分布。.最后对病例组的相关危险因素进行Logistic回归分析。结果： 1.病例组与对照组的一般情况比较,在性别、年龄上无统计学差异,p0.05,而在BMI、高血压、糖尿病病史这些方面有统计学差异,p0.05。 2.病例组及对照组中染色体9p21位点rs7049105(G/A)、rs1333035(T/C)、rs10757274(A/G)均存在多态性。rs647188位点只检测到等位基因A,故不存在多态性。 3.病例组与对照组间rs10757274位点的多态性分布比较未发现统计学显著性差异(p0.05),但在PUBMED数据库中检索以下关键词："rs10757274"、"9p21.3"、"ANRIL",筛查到7项结论不相一致的rs10757274位点与LAS相关性的病例对照研究,结合本次研究最终纳入8项研究进行Meta分析后,总样本量达23372例(病例组：5311例,对照组：18061例),rs10757274位点在显性模型(OR=1.23,95%CI=1.08-1.41)、隐性模型(OR=1.28,95%CI=1.01-1.61)、等位基因模型(OR=1.10,95%CI=1.06-1.14)中均与LAS呈现相关性。 4.病例组与对照组间rs7049105和rs1333035位点的多态性分布比较结果如下：①病例组与对照组1间、病例组与对照组3间rs7049105和rs1333035位点的多态性分布比较未发现统计学显著性差异(p0.05)。②病例组与对照组2间rs7049105位点的多态性分布比较未发现统计学显著性差异(p0.05),病例组与对照组2间rs1333035位点的基因型频率分布比较发现有统计学显著性差异(p=0.039),其中rs1333035位点在显性模型(CT+TT/CC)中表现出与LAS相关的倾向(p=0.144, OR=0.382,95%CI=0.122-1.192),故我们猜测rs1333035的CC基因型可能在有头颈部动脉粥样硬化证据的人群中是LAS的保护性因素。 5.对病例组建立多因素Logistic回归方程分析显示,经校正后纳入方程的为高血压病史、糖尿病病史、BMI。rs1333035多态性位点未纳入回归方程。结论 1.染色体9p21的rs1333035多态性在湖南长沙地区有头颈部动脉粥样硬化证据的汉族人群中与LAS相关,rs1333035位点的CC基因型可能在湖南长沙地区有头颈部动脉粥样硬化证据的汉族人群中是LAS的保护性因素。 2.染色体9p21的rs10757274、rs7049105多态性与湖南长沙地区汉族人群LAS不相关,在湖南长沙地区汉族人群中rs647188不存在多态性。
[Abstract]:Objective : To investigate the association of rs7049105 , rs647188 , rs1333035 , rs1333035 , rs10757274 and rs1333035 of chromosome 9p21 , with large - artery atherosclerosis cerebral infarction ( LAS ) in the Han population in Changsha , Hunan Province .
To investigate the correlation between rs7049105 , rs647188 and rs1333035 locus in the population with evidence of atherosclerosis in the head and neck , and provide theoretical basis for the diagnosis and treatment of LAS .

Methods : A case - control study was used to collect 233 samples from the Han population in Changsha , Hunan . 233 samples were collected in the control group , and the samples were analyzed by matrix - assisted laser scanning inoization - time of flight mass spectrometry ( MALDI - TOF - MS ) . The polymorphism of rs10757274 was analyzed by matrix - assisted laser scanning inoization - time of flight mass spectrometry ( MALDI - TOF - MS ) . Finally , Logistic regression analysis was performed on the relevant risk factors of the case group .

Results :

1 . There was no statistical difference between the case group and the control group , and there was no statistical difference between the case group and the control group , p < 0.05 , while there was statistical difference in BMI , hypertension and diabetes history , p < 0.05 .

2 . There was polymorphism in rs7049105 ( G / A ) , rs1333035 ( T / C ) , rs10757274 ( A / G ) in both case group and control group . rs647188 locus only detected allele A , so there was no polymorphism .

3 . There was no statistically significant difference between case group and control group rs10757274 . However , in PUBMED database , the following keywords were retrieved : " rs10757274 " , " 9p21 . 3 " , " ANDS " , screening to 7 non - consistent rs10757274 sites and LAS - related case - control study . The rs10757274 site was associated with LAS in the dominant model ( OR = 1.23 , 95 % CI = 1.08 - 1.41 ) , recessive model ( OR = 1.28 , 95 % CI = 1.01 - 1.61 ) , allele model ( OR = 1.10 , 95 % CI = 1.06 - 1.14 ) .

4 . The polymorphism distribution of rs7049105 and rs1333035 loci between case group and control group showed no significant difference ( p = 0.039 ) . There was no significant difference ( p = 0.039 ) between case group and control group 2 rs7049105 locus . Among them , rs1333035 locus showed a significant difference in genotype frequency distribution ( p = 0.144 , OR = 0.382 , 95 % CI = 0.122 - 1.192 ) in dominant model ( CT + TT / CC ) . Therefore , we hypothesized that rs1333035 CC genotype might be a protective factor for LAS in the population with evidence of carotid atherosclerosis .

5 . A multivariate logistic regression equation was established for the case group , and the regression equation was not included in the history of hypertension , history of diabetes , BMI and rs1333035 after correction .

Conclusion

1 . The rs1333035 polymorphism of chromosome 9p21 was associated with LAS in Han population with evidence of carotid atherosclerosis in Changsha , Hunan Province . The CC genotype of rs1333035 locus could be the protective factor of LAS in Han population with evidence of carotid atherosclerosis in Changsha , Hunan Province .

2 . rs10757274 , rs7049105 polymorphism of chromosome 9p21 was not related to LAS in Han population in Changsha , Hunan Province , and no polymorphism was found in rs647188 in Han population in Changsha .
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R743.3

【参考文献】