ORP9基因多态性与脑梗死的相关性研究
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摘要
研究背景和目的
氧化固醇结合蛋白相关蛋白-9(Oxysterol-binding protein-related protein9,ORP9)是与动脉粥样硬化病灶形成及血脂、血糖代谢都相关的一类固醇转运蛋白,目前国内外均未见其基因多态性的相关性研究,本实验在国内外首次研究ORP9rs856600和rs768529多态位点基因型和等位基因频率在中国湖南汉族人群中的分布,并首次分析其多态性与脑梗死的相关性,同时探讨该基因多态性与高血压、颈动脉粥样硬化及血糖、血脂代谢的关系。
研究方法
在中南大学湘雅医院就诊的湖南汉族人群中选取动脉粥样硬化血栓性和小动脉闭塞性脑梗死患者作为脑梗死组,另选年龄和性别匹配的健康者作为对照组,各研究对象之间无血缘关系。仔细询问病史并记录检查检验结果,进行病例-对照研究。每位研究对象都于清晨抽取空腹静脉血,采用酚／氯仿法提取DNA,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析技术检测ORP9基因上rs856600及rs768529两个SNP位点的基因型及等位基因频率的分布情况,使用spss17.0软件分析该多态性与脑梗死发病及血压、血脂、血糖、颈动脉粥样硬化的相关性。Rs856600研究对象共406人：(1)对照组151例,其中男性94例,女性57例,平均年龄59士9.50岁；(2)脑梗死组共255例,男性167例,女性88例,平均年龄60士10.29岁。Rs768529研究对象共422人：(1)对照组133例,其中男性88例,女性45例,平均年龄58士10.75岁；(2)脑梗死组共289例,男性193例,女性96例,平均年龄60士10.80岁。
结果
1.rs856600和rs768529基因型及等位基因频率在脑梗死组和对照组之间以及AT组、SAD组和对照组之间分布无显著性差异(P>0.05),二元logistic回归分析未发现任何一种基因型能增加或减少脑梗死发生的风险(P>0.05)；
2.rs856600和rs768529基因型及等位基因频率在脑梗死组和对照组各自的高血压亚组和非高血压亚组之间无显著性差异(P>0.05);rs856600和rs768529多态位点基因型及等位基因频率在脑梗死组和对照组各自的糖尿病亚组和非糖尿病亚组之间无显著性差异(P>0.05)；
3.在脑梗死组和对照组中,rs856600的T等位基因(CT+TT)携带者与CC基因型携带者相比,rs768529的A等位基因(AA+AT)携带者与TT基因型携带者相比,血压、空腹血糖、TG、TC、HDL、LDL水平均无显著性差异(P>0.05)。
4.rs856600基因型和等位基因频率在AS和WAS两个亚组之间、SP和VP两个亚组之间分布不存在显著性差异(P>0.05)；rs768529基因型和等位基因频率在WAS和AS两亚组间分布不存在统计学差异(P>0.05),在脑梗死组AS患者的VP亚组中显著高于SP亚组(P<0.05)。
结论
1.rs856600和rs768529多态性与中国湖南地区汉族人群中脑梗死的发病可能不相关；
2.rs768529的T等位基因可能是中国湖南地区汉族人群颈动脉易损斑块形成的一个危险因素；
3.rs856600多态性与中国湖南地区汉族人群的颈动脉易损斑块形成可能不相关；
4.rs856600和rs768529多态性与中国湖南地区汉族脑梗死人群和正常人群中高血压的发生及血脂血糖代谢可能不相关;
Background and Objeetives
Oxysterol-binding protein-related protein9(ORP9) was a kind of sterol transporter which was related with atherosclerosis、lipids and glucose.There was no reports about the gene polymorphism of ORP9home and abroad. We are the first to investigate the genotypic and allelic distributions of ORP9in Hunan Han population,and first analysis the association of the ORP9gene polymorphisms with cerebral infarction, hypertension, the metabolism of the blood lipid and blood sugar and the formation of carotid atherosclerosis.
Methods
In this study,we choose the subjects from the Hunan Han population that had been to Xiangya Hospital of Central South University. Atherothrombosis cerebral infarction and Small Artery Disease patients were chosen as CI group,age-and sex-matched healthy individuals were chosen as the control group.There were no phylogenetic relationships among the subjects.We asked the case history and recorded the examination results seriously.We collected fasting venous blood from every subject early in the moring and obtained DNA from the blood samples using Phenol/chloroform method.By using PCR-RFLP method, we detected the genotypic and allelic distributions of rs856600and rs768529and analysis the association of the polymorphisms with cerebral infarction, hypertension, the metabolism of the blood lipid and blood sugar and the formation of carotid atherosclerosis.For rs856600,objects studied were composed of406individuals totally:(1)control group was made up of94males and57females,totally151individuals,with the mean age59±9.5years;(2)CI group was composed of167males and88females,totally255individuals,with the mean age60±10.29years.For rs768529, objects studied were composed of406individuals totally:(1)control group was made up of88males and45females,totally133individuals,with the mean age58±10.75years;(2)CI group was composed of193males and96females,totally289individuals,with the mean age60±10.80years.
Results
1. The genotypic and allelic distributions of rs856600and rs768529had no significant differences between the CI group and the control group、the AT、SAD group and the control group (P>0.05).Logistic rergression analysis showed that both the genotypes and the alleles frequency could not increase the risk of the onset of CI(P>0.05).
2. The genotypic and allelic distributions of rs856600and rs768529in the CI group and the control group had no significant differences between the hypertension subgroup and the non-hypertension subgroup,either between the diabetes supgroup and the non-diabetes group(P>0.05).
3. In the control group and the CI group,the hypertention,the serum level of FBS,TG,TC,HDL and LDL of had no significant differences between the T allele(GC+CC) carriers and the TT genetype carriers for rs856600,either between the T allele(GC+CC) carriers and the TT genetype carriers for rs768529.
4. The genotypic and allelic distributions of rs856600had no significant differences between the WAS and AS、the SP and VP subgroup (p>0.05); The genotypic and allelic distributions of rs768529had no significant differences between the WAS and AS subgroup (p>0.05),but the frequency of T allele is higher of the VP subgroup than the SP subgroup (p<0.05) in the CI group.
Conclusions
1.Association of the rs856600and rs768529Polymorphisms with cerebral infarction in Hunan Han Population may not exist.
2. T allele of rs768529may be a risk factor for the formation of the carotid vulnerable plaque in Hunan Han population.
3. Association of the rs856600polymorphisms and the formation of the carotid vulnerable plaque in Hunan Han population may not exist;
4.Association of rs856600and rs768529polymophisms with the occurrence of hypertention and the metabolism of blood lipid and blood sugar in the CI and healty Hunan Han population may not exist.
氧化固醇结合蛋白相关蛋白-9(Oxysterol-binding protein-related protein9,ORP9)是与动脉粥样硬化病灶形成及血脂、血糖代谢都相关的一类固醇转运蛋白,目前国内外均未见其基因多态性的相关性研究,本实验在国内外首次研究ORP9rs856600和rs768529多态位点基因型和等位基因频率在中国湖南汉族人群中的分布,并首次分析其多态性与脑梗死的相关性,同时探讨该基因多态性与高血压、颈动脉粥样硬化及血糖、血脂代谢的关系。
研究方法
在中南大学湘雅医院就诊的湖南汉族人群中选取动脉粥样硬化血栓性和小动脉闭塞性脑梗死患者作为脑梗死组,另选年龄和性别匹配的健康者作为对照组,各研究对象之间无血缘关系。仔细询问病史并记录检查检验结果,进行病例-对照研究。每位研究对象都于清晨抽取空腹静脉血,采用酚／氯仿法提取DNA,应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析技术检测ORP9基因上rs856600及rs768529两个SNP位点的基因型及等位基因频率的分布情况,使用spss17.0软件分析该多态性与脑梗死发病及血压、血脂、血糖、颈动脉粥样硬化的相关性。Rs856600研究对象共406人：(1)对照组151例,其中男性94例,女性57例,平均年龄59士9.50岁；(2)脑梗死组共255例,男性167例,女性88例,平均年龄60士10.29岁。Rs768529研究对象共422人：(1)对照组133例,其中男性88例,女性45例,平均年龄58士10.75岁；(2)脑梗死组共289例,男性193例,女性96例,平均年龄60士10.80岁。
结果
1.rs856600和rs768529基因型及等位基因频率在脑梗死组和对照组之间以及AT组、SAD组和对照组之间分布无显著性差异(P>0.05),二元logistic回归分析未发现任何一种基因型能增加或减少脑梗死发生的风险(P>0.05)；
2.rs856600和rs768529基因型及等位基因频率在脑梗死组和对照组各自的高血压亚组和非高血压亚组之间无显著性差异(P>0.05);rs856600和rs768529多态位点基因型及等位基因频率在脑梗死组和对照组各自的糖尿病亚组和非糖尿病亚组之间无显著性差异(P>0.05)；
3.在脑梗死组和对照组中,rs856600的T等位基因(CT+TT)携带者与CC基因型携带者相比,rs768529的A等位基因(AA+AT)携带者与TT基因型携带者相比,血压、空腹血糖、TG、TC、HDL、LDL水平均无显著性差异(P>0.05)。
4.rs856600基因型和等位基因频率在AS和WAS两个亚组之间、SP和VP两个亚组之间分布不存在显著性差异(P>0.05)；rs768529基因型和等位基因频率在WAS和AS两亚组间分布不存在统计学差异(P>0.05),在脑梗死组AS患者的VP亚组中显著高于SP亚组(P<0.05)。
结论
1.rs856600和rs768529多态性与中国湖南地区汉族人群中脑梗死的发病可能不相关；
2.rs768529的T等位基因可能是中国湖南地区汉族人群颈动脉易损斑块形成的一个危险因素；
3.rs856600多态性与中国湖南地区汉族人群的颈动脉易损斑块形成可能不相关；
4.rs856600和rs768529多态性与中国湖南地区汉族脑梗死人群和正常人群中高血压的发生及血脂血糖代谢可能不相关;
Background and Objeetives
Oxysterol-binding protein-related protein9(ORP9) was a kind of sterol transporter which was related with atherosclerosis、lipids and glucose.There was no reports about the gene polymorphism of ORP9home and abroad. We are the first to investigate the genotypic and allelic distributions of ORP9in Hunan Han population,and first analysis the association of the ORP9gene polymorphisms with cerebral infarction, hypertension, the metabolism of the blood lipid and blood sugar and the formation of carotid atherosclerosis.
Methods
In this study,we choose the subjects from the Hunan Han population that had been to Xiangya Hospital of Central South University. Atherothrombosis cerebral infarction and Small Artery Disease patients were chosen as CI group,age-and sex-matched healthy individuals were chosen as the control group.There were no phylogenetic relationships among the subjects.We asked the case history and recorded the examination results seriously.We collected fasting venous blood from every subject early in the moring and obtained DNA from the blood samples using Phenol/chloroform method.By using PCR-RFLP method, we detected the genotypic and allelic distributions of rs856600and rs768529and analysis the association of the polymorphisms with cerebral infarction, hypertension, the metabolism of the blood lipid and blood sugar and the formation of carotid atherosclerosis.For rs856600,objects studied were composed of406individuals totally:(1)control group was made up of94males and57females,totally151individuals,with the mean age59±9.5years;(2)CI group was composed of167males and88females,totally255individuals,with the mean age60±10.29years.For rs768529, objects studied were composed of406individuals totally:(1)control group was made up of88males and45females,totally133individuals,with the mean age58±10.75years;(2)CI group was composed of193males and96females,totally289individuals,with the mean age60±10.80years.
Results
1. The genotypic and allelic distributions of rs856600and rs768529had no significant differences between the CI group and the control group、the AT、SAD group and the control group (P>0.05).Logistic rergression analysis showed that both the genotypes and the alleles frequency could not increase the risk of the onset of CI(P>0.05).
2. The genotypic and allelic distributions of rs856600and rs768529in the CI group and the control group had no significant differences between the hypertension subgroup and the non-hypertension subgroup,either between the diabetes supgroup and the non-diabetes group(P>0.05).
3. In the control group and the CI group,the hypertention,the serum level of FBS,TG,TC,HDL and LDL of had no significant differences between the T allele(GC+CC) carriers and the TT genetype carriers for rs856600,either between the T allele(GC+CC) carriers and the TT genetype carriers for rs768529.
4. The genotypic and allelic distributions of rs856600had no significant differences between the WAS and AS、the SP and VP subgroup (p>0.05); The genotypic and allelic distributions of rs768529had no significant differences between the WAS and AS subgroup (p>0.05),but the frequency of T allele is higher of the VP subgroup than the SP subgroup (p<0.05) in the CI group.
Conclusions
1.Association of the rs856600and rs768529Polymorphisms with cerebral infarction in Hunan Han Population may not exist.
2. T allele of rs768529may be a risk factor for the formation of the carotid vulnerable plaque in Hunan Han population.
3. Association of the rs856600polymorphisms and the formation of the carotid vulnerable plaque in Hunan Han population may not exist;
4.Association of rs856600and rs768529polymophisms with the occurrence of hypertention and the metabolism of blood lipid and blood sugar in the CI and healty Hunan Han population may not exist.
引文
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