ALOX5AP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分析

doi:10.3969/j.issn.1673-8640.2017.06.007

摘要/Abstract

摘要：

目的探讨5-脂氧合酶激活蛋白（ALOX5AP）基因单核苷酸多态性与缺血性脑卒中患者颈动脉斑块的关系,为颈动脉斑块的缺血性脑卒中早期诊断、治疗和发病机制研究提供依据。方法选取737例缺血性脑卒中患者,按有无颈动脉斑块分为斑块组和无斑块组,应用多重聚合酶链反应（PCR）及基因序列分析技术分析各组患者ALOX5AP基因8个位点多态性分布情况。结果斑块组的甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、非高密度脂蛋白胆固醇（non-HDL-C）、收缩压和血葡萄糖（Glu）水平均明显高于无斑块组（P<0.05）。对ALOX5AP基因8个位点基因型和等位基因频率分析发现,斑块组与无斑块组间差异无统计学意义（P>0.05）。ALOX5AP基因8个位点组成的2个单倍型构成在斑块组与无斑块组间差异无统计学意义（P>0.05）。结论 ALOX5AP基因多态性与缺血性脑卒中患者颈动脉斑块形成无关。

关键词: 5-脂氧合酶激活蛋白, 缺血性脑卒中, 基因型频率, 等位基因频率

Abstract:

Objective To study the correlation of 5-lipoxygenase activating protein （ALOX5AP）gene single nucleotide polymorphisms and carotid plaques in patients with ischemic cerebral stroke,and to provide a reference for the early diagnosis,treatment and pathogenesis of carotid plaque-related ischemic cerebral stroke. Methods A total of 737 patients with ischemic cerebral stroke were enrolled and classified into carotid plaque group and non-carotid plaque group. Multiple polymerase chain reaction （PCR） and gene sequencing were used to analyze the 8 locus polymorphisms of ALOX5AP gene. Results Triglyceride （TG）,low-density lipoprotein cholesterol （LDL-C）,non-high-density lipoprotein cholesterol （non-HDL-C）,systolic blood pressure and blood glucose（Glu） levels in carotid plaque group were higher than those in non-carotid plaque group （P<0.05）. There was no statistical significance for the genotypes and allele frequencies of 8 loci of ALOX5AP gene between carotid plaque and non-carotid plaque groups （P>0.05）. There was no statistical significance for 8 loci of ALOX5AP gene in the formation of 2 haplotypes between carotid plaque and non-carotid plaque groups （P>0.05）. Conclusions ALOX5AP gene polymorphisms have no relationship with carotid plaque formation in ischemic cerebral stroke.

Key words: 5-Lipoxygenase activating protein, Ischemic cerebral stroke, Genotype frequency, Allele frequency

中图分类号:

R446.1

王文惠, 杨卫华, 堵一乔, 梁发东, 杨振华. ALOX5AP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分析[J]. 检验医学, 2017, 32(6): 474-480.

WANG Wenhui, YANG Weihua, DU Yiqiao, LIANG Fadong, YANG Zhenhua. Correlation of ALOX5AP gene single nucleotide polymorphisms and carotid plaques in patients with ischemic cerebral stroke[J]. Laboratory Medicine, 2017, 32(6): 474-480.

图/表 8

参考文献 20

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基因多态性位点	上游引物	下游引物	长度（bp）
rs10507391	GGTCCCTTTGAAACCACAGA	GAATGGCATTTTGGGGTATG	260
rs4075132	ACCAGAAAGGCTCAGCTTCA	TCCGCCTGTACCCAGAATAC	280
rs4075131	TGGACAGATGCTGGTGATGT	GGAGCCCTGTGTGAAATCAT	245
rs9578196	TCTCTCCAGCTCCCTCTCAA	TTGTGGCTGTCAGGACTCAG	300
rs9315048	GCAGAAAGGAAACCCAAAGA	AATGGGAACCCAATTGAACA	241
rs9315045	CACGCCCAGCTAATTTTTGT	TGACCTTGGGACTTTCAACC	223
rs9551963	ATTTTCAACCCTGCCGTCTA	CCCTGGATCAAGGATGACAC	289
rs12429692	ATGTCCAAGCCTCTCTTTGC	TGCCCAATCACAGAAAATCA	291

基因多态性位点	上游引物	下游引物	长度（bp）
rs10507391	GGTCCCTTTGAAACCACAGA	GAATGGCATTTTGGGGTATG	260
rs4075132	ACCAGAAAGGCTCAGCTTCA	TCCGCCTGTACCCAGAATAC	280
rs4075131	TGGACAGATGCTGGTGATGT	GGAGCCCTGTGTGAAATCAT	245
rs9578196	TCTCTCCAGCTCCCTCTCAA	TTGTGGCTGTCAGGACTCAG	300
rs9315048	GCAGAAAGGAAACCCAAAGA	AATGGGAACCCAATTGAACA	241
rs9315045	CACGCCCAGCTAATTTTTGT	TGACCTTGGGACTTTCAACC	223
rs9551963	ATTTTCAACCCTGCCGTCTA	CCCTGGATCAAGGATGACAC	289
rs12429692	ATGTCCAAGCCTCTCTTTGC	TGCCCAATCACAGAAAATCA	291

位点	探针序列	长度（bp）
rs10507391_modify	P-TAGAATTGCAAAGAGAGGCTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-FAM
rs10507391_A	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTATGGTTGCAACATTGAGGTTAAT	109
rs10507391_T	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTATGGTTGCAACATTGAGGTTAAA	111
rs4075132_modify	P-TAAGCCATTTGTTCCCTCTCTGAGCTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-FAM
rs4075132_C	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTGGCTCAAGAAAATGGTGGCCTAAG	158
rs4075132_T	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTGGCTCAAGAAAATGGTGGCCTAAA	160
rs4075131_modify	P-AAAAATGTTTGGGTCAGAAAGCCACTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-FAM
rs4075131_A	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTAACTTTGTTGTGTGTAATTTAGTAT	174
rs4075131_G	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTAACTTTGTTGTGTGTAATTTAGTAC	176
rs9578196_modify	P-AAATCTCACCACTCACCTCAATCTGTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-FAM
rs9578196_C	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTCTATCTGTCAAAAAGAATTCG	150
rs9578196_T	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTCTATCTGTCAAAAAGAATTCA	152
rs9315048_modify	P-CTAAAATTCTGATGTTCGTTCAAGCTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-FAM
rs9315048_G	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTCACCAGGAGGGTACAAATCCAGCCC	174
rs9315048_T	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTCACCAGGAGGGTACAAATCCAGCCA	176
rs9315045_modify	P-TGTTTTACAGATAAGCAAAGTGAGTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-FAM
rs9315045_A	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTAGAAATACATACTATTATTTATTCT	178
rs9315045_G	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTAGAAATACATACTATTATTTATTCC	180
rs9551963_modify	P-AGCAATTCCTCCTCGGTTGGTGAGGTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-FAM
rs9551963_A	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTAAATTCCGGGGGAAGGATCTCATCT	182
rs9551963_C	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTAAATTCCGGGGGAAGGATCTCATCG	184
rs12429692_modify	P-CCCCAAAATGCCATTCTGAATTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-FAM
rs12429692_A	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTCCCTGCCTTTCTTCTTCCTCATT	77
rs12429692_T	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTCCCTGCCTTTCTTCTTCCTCATA	79

位点	探针序列	长度（bp）
rs10507391_modify	P-TAGAATTGCAAAGAGAGGCTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-FAM
rs10507391_A	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTATGGTTGCAACATTGAGGTTAAT	109
rs10507391_T	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTATGGTTGCAACATTGAGGTTAAA	111
rs4075132_modify	P-TAAGCCATTTGTTCCCTCTCTGAGCTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-FAM
rs4075132_C	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTGGCTCAAGAAAATGGTGGCCTAAG	158
rs4075132_T	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTGGCTCAAGAAAATGGTGGCCTAAA	160
rs4075131_modify	P-AAAAATGTTTGGGTCAGAAAGCCACTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-FAM
rs4075131_A	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTAACTTTGTTGTGTGTAATTTAGTAT	174
rs4075131_G	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTAACTTTGTTGTGTGTAATTTAGTAC	176
rs9578196_modify	P-AAATCTCACCACTCACCTCAATCTGTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-FAM
rs9578196_C	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTCTATCTGTCAAAAAGAATTCG	150
rs9578196_T	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTCTATCTGTCAAAAAGAATTCA	152
rs9315048_modify	P-CTAAAATTCTGATGTTCGTTCAAGCTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-FAM
rs9315048_G	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTCACCAGGAGGGTACAAATCCAGCCC	174
rs9315048_T	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTCACCAGGAGGGTACAAATCCAGCCA	176
rs9315045_modify	P-TGTTTTACAGATAAGCAAAGTGAGTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-FAM
rs9315045_A	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTAGAAATACATACTATTATTTATTCT	178
rs9315045_G	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTAGAAATACATACTATTATTTATTCC	180
rs9551963_modify	P-AGCAATTCCTCCTCGGTTGGTGAGGTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-FAM
rs9551963_A	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTAAATTCCGGGGGAAGGATCTCATCT	182
rs9551963_C	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTAAATTCCGGGGGAAGGATCTCATCG	184
rs12429692_modify	P-CCCCAAAATGCCATTCTGAATTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT-FAM
rs12429692_A	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTCCCTGCCTTTCTTCTTCCTCATT	77
rs12429692_T	TTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTCCCTGCCTTTCTTCTTCCTCATA	79

组别	例数	TG（mmol/L）	TC（mmol/L）	HDL-C（mmol/L）	LDL-C（mmol/L）
无斑块组	306	1.48（1.09~2.07）	4.48（3.77~5.18）	1.03（0.89~1.26）	2.80（2.14~3.44）
斑块组	431	1.63（1.20~2.39）	4.75（3.92~5.40）	1.03（0.88~1.18）	3.06（2.43~3.58）
统计值		8.626 2	5.738 0	0.838 7	7.916 4
P值		0.003 3	0.016 6	0.359 8	0.004 9
无斑块组	3.39（2.74~4.02）		18.7（16.6~20.0）	10.7（10.4~12.0）	5.16（4.60~6.11）
斑块组	3.71（2.87~4.33）		18.7（17.3~20.8）	10.7（10.0~12.0）	5.44（4.75~7.30）
统计值	9.645 6		13.471 4	0.008 2	13.892 5
P值	0.001 9		0.000 2	0.928 0	0.000 2