ApoH基因单核苷酸多态性与缺血性脑卒中患者颈动脉斑块的相关性研究

doi:10.3969/j.issn.1673-8640.2017.12.004

摘要/Abstract

摘要：

目的研究载脂蛋白H（ApoH）基因单核苷酸多态性（SNP）与缺血性脑卒中（ICS）患者颈动脉斑块的相关性。方法选取上海交通大学医学院附属瑞金医院及上海市闵行区中心医院神经内科住院的ICS中确诊患者,其中ICS伴颈动脉斑块431例（斑块组）,不伴颈动脉斑块306例（对照组）。采用多重聚合酶链反应（PCR）及基因序列分析技术,对ApoH基因SNP位点（rs8178842、rs6933、rs4791079、rs2873966和rs1801690）进行2个组间基因型及等位基因频率的差异比较,并对相对风险进行评估。结果经统计分析发现,斑块组的甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、非高密度脂蛋白胆固醇（non-HDL-C）、收缩压和血糖均明显高于对照组（P<0.05）。对ApoH基因SNP基因型频率在斑块组与对照组间进行比较分析发现,斑块组rs4791079位点CA、CA/AA基因型频率为15.3%、16.5%,显著高于对照组（8.8%、8.8%）,差异具有统计学意义（P=0.008、P=0.022）。而斑块组rs1801690位点GC/CC基因型频率（8.8%）显著低于对照组（13.4%）,差异具有统计学意义（P=0.049）。对ApoH基因SNP等位基因频率在斑块组与对照组间进行比较分析发现,斑块组rs4791079位点A等位基因频率（8.8%）显著高于对照组（4.4%）,差异具有统计学意义（P=0.001）。似然比分析发现,携带A等位基因者发生斑块的危险性显著增加[比值比（OR）=2.095,95%可信区间（CI）1.333~3.292]。斑块组rs1801690位点C等位基因频率（4.4%）显著低于对照组（7.0%）,差异具有统计学意义（P=0.030）。相对风险度分析发现,携带C等位基因者发生斑块的危险性降低（OR=0.610,95%CI 0.389~0.956）。结论 ApoH基因rs4791079位点和rs1801690位点基因多态性与ICS伴颈动脉斑块的发病具有相关性。

关键词: 载脂蛋白H, 缺血性脑卒中, 单核苷酸多态性, 基因型频率, 颈动脉斑块

Abstract:

Objective To study the correlation of apopoprotein H（ApoH） gene single nucleotide polymorphisms（SNP）and carotid plaques in patients with ischemic cerebral stroke（ICS）. Methods A total of 737 patients with ICS were enrolled from Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine and Department of Neurology of Central Hospital of Shanghai Minhang District. They were classified into carotid plaque group（431 cases） and non-carotid plaque group（306 cases）（control group）. By multiple polymerase chain reaction（PCR） and sequence analysis,the genotype and allele frequencies of ApoH gene SNP loci（rs8178842,rs6933,rs4791079,rs2873966 and rs1801690） between the 2 groups were compared,and the relative risk was evaluated. Results In carotid plaque group,triglyceride（TG）,total cholesterol（TC）,low-density lipoprotein cholesterol（LDL-C）,non-high-density lipoprotein cholesterol（non-HDL-C）,systolic blood pressure and blood glucose were higher than those in control group（P<0.05）. In carotid plaque group,rs4791079 locus CA and CA/AA genotype frequencies were 15.3% and 16.5%,which were higher than those in control group（8.8% and 8.8%）（P=0.008,P=0.022）. In carotid plaque group,rs1801690 locus GC/CC genotype frequency was 8.8%,which was lower than that in control group（13.4%）（P=0.049）. In carotid plaque group,rs4791079 locus A allele frequency（8.8%） was higher than that in control group（4.4%）（P=0.001）. The relative risk analysis found that carrying A allele increased the risk of carotid plaque [odds ratio（OR）=2.095,95% confidence interval（CI）1.333-3.292]. In carotid plaque group,rs1801690 locus C allele frequency（4.4%）was lower than that in control group（7.0%）（P=0.030）. The relative risk analysis found that carrying C allele decreased the risk of carotid plaque（OR=0.610,95%CI 0.389-0.956）. Conclusions ApoH gene rs4791079 and rs1801690 loci have correlations with carotid plaques in patients with ICS.

Key words: Apopoprotein H, Ischemic cerebral stroke, Single nucleotide polymorphism, Genotype frequency, Carotid plaque

中图分类号:

R446.1

舒铭, 王燕, 陈宁, 吴洁敏, 倪培华. ApoH基因单核苷酸多态性与缺血性脑卒中患者颈动脉斑块的相关性研究[J]. 检验医学, 2017, 32(12): 1089-1094.

SHU Ming, WANG Yan, CHEN Ning, WU Jiemin, NI Peihua. Correlation of ApoH gene single nucleotide polymorphisms and carotid plaques in patients with ischemic cerebral stroke[J]. Laboratory Medicine, 2017, 32(12): 1089-1094.

图/表 6

参考文献 14

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SNP位点	上游引物	下游引物	长度（bp）
rs2873966	GCCAGTTGGTGATGAATCCT	TGCAAAAACCAACCACACAT	269
rs1801690	CTCCCCCAACAGAACACAGT	TGCCAACTTCACAGCCATAG	274
rs6933	CTCCCCCAACAGAACACAGT	TGCCAACTTCACAGCCATAG	274
rs4791079	TCACCCCAAGTGACAAAACA	TAAACGCTGGCCATTACACA	192
rs8178842	CCTGGGCAACAAGAGTGAA	GAGCTGTGATCACGCCACT	292

SNP位点	上游引物	下游引物	长度（bp）
rs2873966	GCCAGTTGGTGATGAATCCT	TGCAAAAACCAACCACACAT	269
rs1801690	CTCCCCCAACAGAACACAGT	TGCCAACTTCACAGCCATAG	274
rs6933	CTCCCCCAACAGAACACAGT	TGCCAACTTCACAGCCATAG	274
rs4791079	TCACCCCAAGTGACAAAACA	TAAACGCTGGCCATTACACA	192
rs8178842	CCTGGGCAACAAGAGTGAA	GAGCTGTGATCACGCCACT	292

SNP位点	探针序列	长度（bp）
rs2873966_modify	P-GAAAAAGTAGGAATAGTTCCTTTTTTTTTTTTTTTTTT-FAM
rs2873966_C	TTTTTTTTTTTTTTTTATGGGAGAGACCATTGAGATACG	77
rs2873966_T	TTTTTTTTTTTTTTTTTTATGGGAGAGACCATTGAGATACA	79
rs1801690_modify	P-AAAAAGCCAGAGAACTGTGTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-FAM
rs1801690_C	TTTTTTTTTTTTTTTTTTTTTTTTTTTACATCGGATGCATCAGTTTTCG	97
rs1801690_G	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTACATCGGATGCATCAGTTTTCC	99
rs6933_modify	P-AAAATGTCACACTTGTTTCTTGTTCTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-TTTTTTTTTTTTTTTTTTTT-FAM
rs6933_A	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT- CTAAGGTGGTTTTCAGATTCCACAT	166
rs6933_G	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-TTCTAAGGTGGTTTTCAGATTCCACAC	168
rs4791079_modify	P-GAGAAAGGGGAAATGTTAGATCTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-TTTTTTTTTTTTTTTTTTTTT-FAM
rs4791079_A	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-TTTTACTTTTCAAACTCTACGAATTGCTT	170
rs4791079_C	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-TTTTTTACTTTTCAAACTCTACGAATTGCTG	172
rs8178842_modify	P-TTCTTAAACAATTATTTATTTGAAATTTTTTTTTTTTTTTTTTTTTTTTGCATCACTCA-FAM
rs8178842_A	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTACTTTCGTTTTTGCTTGTTCAGGTT	87
rs8178842_G	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTACTTTCGTTTTTGCTTGTTCAGGTC	89

SNP位点	探针序列	长度（bp）
rs2873966_modify	P-GAAAAAGTAGGAATAGTTCCTTTTTTTTTTTTTTTTTT-FAM
rs2873966_C	TTTTTTTTTTTTTTTTATGGGAGAGACCATTGAGATACG	77
rs2873966_T	TTTTTTTTTTTTTTTTTTATGGGAGAGACCATTGAGATACA	79
rs1801690_modify	P-AAAAAGCCAGAGAACTGTGTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-FAM
rs1801690_C	TTTTTTTTTTTTTTTTTTTTTTTTTTTACATCGGATGCATCAGTTTTCG	97
rs1801690_G	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTACATCGGATGCATCAGTTTTCC	99
rs6933_modify	P-AAAATGTCACACTTGTTTCTTGTTCTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-TTTTTTTTTTTTTTTTTTTT-FAM
rs6933_A	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT- CTAAGGTGGTTTTCAGATTCCACAT	166
rs6933_G	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-TTCTAAGGTGGTTTTCAGATTCCACAC	168
rs4791079_modify	P-GAGAAAGGGGAAATGTTAGATCTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-TTTTTTTTTTTTTTTTTTTTT-FAM
rs4791079_A	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-TTTTACTTTTCAAACTCTACGAATTGCTT	170
rs4791079_C	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-TTTTTTACTTTTCAAACTCTACGAATTGCTG	172
rs8178842_modify	P-TTCTTAAACAATTATTTATTTGAAATTTTTTTTTTTTTTTTTTTTTTTTGCATCACTCA-FAM
rs8178842_A	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTACTTTCGTTTTTGCTTGTTCAGGTT	87
rs8178842_G	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTACTTTCGTTTTTGCTTGTTCAGGTC	89

SNP位点	对照组（306例）		斑块组（431例）
SNP位点	统计值	P值	统计值	P值
rs8178842	0.787 1	0.375 0	0.967 8	0.325 2
rs2873966	0.028 1	0.866 8	0.070 9	0.790 1
rs4791079	0.651 8	0.419 5	0.976 8	0.323 0
rs6933	1.058 8	0.303 5	0.005 4	0.941 3
rs1801690	0.183 4	0.668 5	0.916 6	0.338 4