载脂蛋白M基因多态性与冠心病的关系研究
摘要
目的通过测定载脂蛋白M(apolipoprotein M,apoM)基因多态性,分析apoM不同基因型与血脂关系,探讨apoM不同位点基因型与冠心病的关系。通过测定血浆apoM的水平,分析其与血脂的相关性,进一步探讨其与冠心病的关系。为冠心病的早期诊断和预防治疗提供理论依据。
方法入选病例组112例及对照组168例,采用等位基因特异性引物PCR检测方法检测apoM基因多态性,采用ELISA方法测定外周血中apoM水平。采用酶法测定甘油三酯(triglyeride,TG)、总胆固醇(total cholesterol,TC),采用直接均相法测定高密度脂蛋白胆固醇(high density lipoprotein-cholesterol,HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein-cholesterol,LDL-C)。
结果
(1) C-1065A位点存在三种不同基因型AA、CA、CC,三种基因型在病例组和对照组间差异有统计学意义(χ~2=11.079,df=2,P=0.004)。病例组A等位基因的频率显著高于对照组,差异有统计学意义(41.5%vs30.4%,χ~2=7.376,df=1,P=0.007)。
(2) T-778C位点存在三种不同基因型TT、TC、CC,三种基因型在病例组和对照组间差异有统计学意义(χ~2=9.548,df=2,P=0.008)。病例组C等位基因的频率显著高于对照组,差异有统计学意义(15.2%vs7.4%,χ~2=8.538,df=1,P=0.003)。
(3) T-778C位点不同基因型与血脂的关系:冠心病组中TC/CC基因型患者胆固醇浓度明显高于TT基因型的患者,差异有统计学意义(4.83±0.41mmol/Lvs4.24±0.96mmol/L t’=-3.475,P=0.001)。对照组中TC/CC基因型胆固醇浓度明显高于TT基因型,差异有统计学意义(4.42±0.29mmol/Lvs3.73±0.58mmol/L t’=-4.441,P<0.001)。而低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、甘油三酯(TG)浓度与基因型差异无统计学意义P>0.05)。
(4)冠心病组apoM浓度显著高于对照组,差异有统计学意义(19.05±2.74mg/Lvs 14.46±2.28mg/L t=7.928,P<0.01)。
(5) C-1065A位点各基因型与apoM的关系:AA基因型人apoM浓度(17.49±4.09mg/L),CA基因型人apoM浓度(17.59±3.42mg/L),CC基因型人apoM浓度(14.76±2.55mg/L),经单因素方差分析:组间和组内比较F=2.689 P=0.075,差异无统计学意义(P>0.05)。T-778C位点各基因型与apoM的关系:TT基因型人apoM浓度(17.24±3.41mg/L),TC基因型和CC基因型人apoM浓度(17.67±3.52mg/L),(t=-0.409 P=0.684)差异无统计学意义(P>0.05)
结论
(1)apoM基因单核苷酸多态性(Single Nucleotide Polymorphisms,SNP)T-778C位点单核苷酸C可能是冠心病的危险因子之一,单核苷酸C可能与血清总胆固醇存在相关性。
(2)apoM基因SNPC-1065A位点单核苷酸A可能是冠心病的危险因子之一。
(3)冠心病患者血浆apoM水平高于对照组。
(4)apoM可能是冠心病的预测因子之一。
Objective To investigate the associations polymorphism of apoM and plasma concentration of apoM with CHD,analyse the relationship between apoM and blood lipid. Method Three groups of subjects were enrolled: group1,patients with coronary heart disease(CHD,n=112);group2, control group who are subjects with normal coronary artery on angiography (NCA,n=168). ApoM genetic polymorphism were measured using an allele gene specific polymerase chain reaction(ASPCR) technique.The concentrations of serum apoM were measured using an ELISA technique.
Results (1)The genotype and allele frequencies of the C-1065A were different in both coronary heart disease and the controls.(χ~2=11.079,df=2,P=0.004). The A allele of the C-1065A SNPs in coronary heart disease patients was significantly higher than that of the healthy controls.(41.5% vs30.4%,χ~2=7.376,df=1,P=0.007).(2)The genotype and allele frequencies of the T-778C were similar in both ischemic stroke patients and the controls.(χ~2=9.548,df=2,P=0.008). The C allele of the T-778C SNPs in coronary heart disease patients was significantly higher than that of the healthy controls.(15.2%vs7.4%,χ~2=8.538,df=1,P=0.003).(3)CHD patients with CT/CC genotype had significantly higher concentrations of TC than those with TT genotypes(t’=-3.475, P=0.001).There is a similar trend in controls ( t’=-4.441, P<0.001). TG, LDL-C and HDL-C concentrations do not correlate with apoM genotypes.(4.)CHD patients with had significantly higher concentrations of apoM than those in the control .(t=7.928, P<0.01).
Conclusion (1) The C allele of the T-778C SNPs is possibly associated with increased risk of CHD. The C allele of the T-778C SNPs is possibly associated with concentrations of TC.(2) The C allele of the C-1065A SNPs is possibly associated with increased risk of CHD.(3) CHD patients with had significantly higher concentrations of apoM than those normal coronary artery on angiography.(4)ApoM is possibly a predictable factor in CHD.
方法入选病例组112例及对照组168例,采用等位基因特异性引物PCR检测方法检测apoM基因多态性,采用ELISA方法测定外周血中apoM水平。采用酶法测定甘油三酯(triglyeride,TG)、总胆固醇(total cholesterol,TC),采用直接均相法测定高密度脂蛋白胆固醇(high density lipoprotein-cholesterol,HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein-cholesterol,LDL-C)。
结果
(1) C-1065A位点存在三种不同基因型AA、CA、CC,三种基因型在病例组和对照组间差异有统计学意义(χ~2=11.079,df=2,P=0.004)。病例组A等位基因的频率显著高于对照组,差异有统计学意义(41.5%vs30.4%,χ~2=7.376,df=1,P=0.007)。
(2) T-778C位点存在三种不同基因型TT、TC、CC,三种基因型在病例组和对照组间差异有统计学意义(χ~2=9.548,df=2,P=0.008)。病例组C等位基因的频率显著高于对照组,差异有统计学意义(15.2%vs7.4%,χ~2=8.538,df=1,P=0.003)。
(3) T-778C位点不同基因型与血脂的关系:冠心病组中TC/CC基因型患者胆固醇浓度明显高于TT基因型的患者,差异有统计学意义(4.83±0.41mmol/Lvs4.24±0.96mmol/L t’=-3.475,P=0.001)。对照组中TC/CC基因型胆固醇浓度明显高于TT基因型,差异有统计学意义(4.42±0.29mmol/Lvs3.73±0.58mmol/L t’=-4.441,P<0.001)。而低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、甘油三酯(TG)浓度与基因型差异无统计学意义P>0.05)。
(4)冠心病组apoM浓度显著高于对照组,差异有统计学意义(19.05±2.74mg/Lvs 14.46±2.28mg/L t=7.928,P<0.01)。
(5) C-1065A位点各基因型与apoM的关系:AA基因型人apoM浓度(17.49±4.09mg/L),CA基因型人apoM浓度(17.59±3.42mg/L),CC基因型人apoM浓度(14.76±2.55mg/L),经单因素方差分析:组间和组内比较F=2.689 P=0.075,差异无统计学意义(P>0.05)。T-778C位点各基因型与apoM的关系:TT基因型人apoM浓度(17.24±3.41mg/L),TC基因型和CC基因型人apoM浓度(17.67±3.52mg/L),(t=-0.409 P=0.684)差异无统计学意义(P>0.05)
结论
(1)apoM基因单核苷酸多态性(Single Nucleotide Polymorphisms,SNP)T-778C位点单核苷酸C可能是冠心病的危险因子之一,单核苷酸C可能与血清总胆固醇存在相关性。
(2)apoM基因SNPC-1065A位点单核苷酸A可能是冠心病的危险因子之一。
(3)冠心病患者血浆apoM水平高于对照组。
(4)apoM可能是冠心病的预测因子之一。
Objective To investigate the associations polymorphism of apoM and plasma concentration of apoM with CHD,analyse the relationship between apoM and blood lipid. Method Three groups of subjects were enrolled: group1,patients with coronary heart disease(CHD,n=112);group2, control group who are subjects with normal coronary artery on angiography (NCA,n=168). ApoM genetic polymorphism were measured using an allele gene specific polymerase chain reaction(ASPCR) technique.The concentrations of serum apoM were measured using an ELISA technique.
Results (1)The genotype and allele frequencies of the C-1065A were different in both coronary heart disease and the controls.(χ~2=11.079,df=2,P=0.004). The A allele of the C-1065A SNPs in coronary heart disease patients was significantly higher than that of the healthy controls.(41.5% vs30.4%,χ~2=7.376,df=1,P=0.007).(2)The genotype and allele frequencies of the T-778C were similar in both ischemic stroke patients and the controls.(χ~2=9.548,df=2,P=0.008). The C allele of the T-778C SNPs in coronary heart disease patients was significantly higher than that of the healthy controls.(15.2%vs7.4%,χ~2=8.538,df=1,P=0.003).(3)CHD patients with CT/CC genotype had significantly higher concentrations of TC than those with TT genotypes(t’=-3.475, P=0.001).There is a similar trend in controls ( t’=-4.441, P<0.001). TG, LDL-C and HDL-C concentrations do not correlate with apoM genotypes.(4.)CHD patients with had significantly higher concentrations of apoM than those in the control .(t=7.928, P<0.01).
Conclusion (1) The C allele of the T-778C SNPs is possibly associated with increased risk of CHD. The C allele of the T-778C SNPs is possibly associated with concentrations of TC.(2) The C allele of the C-1065A SNPs is possibly associated with increased risk of CHD.(3) CHD patients with had significantly higher concentrations of apoM than those normal coronary artery on angiography.(4)ApoM is possibly a predictable factor in CHD.
引文
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[21]Nakamura Y,Kotitel,Gan Y,spencer TA,Fielding CJ,Fielding PE.Molecular mechanism reaction of pre-beta-migrating high-density lipoprotein with plasma lecithin/cholesterol acytransferase[J].Biochemistry,2004,43(46):14 811-820.
[22]ChauP, Nakamura Y, Fielding CJ, Fielding PE. Mechanism of prebeta-HDL formation and activation [J].Biochemistry, 2006, 45(12):3 981-987.
[23]Wolfrum C, Poy MN, Stoffel M. Apolipoprotein M is required for prebeta-HDL formation and cholesterol efflux to HDL and protects against atherosclerosis [J]. Nat Med, 2005, 11(4):418-422.
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[27]Guo q. A prospective evaluation of apolipoprotein M gene T-778C polymorphism in relation to coronary artery disease in Han Chinese Clinical Biochemistry 40 (2007) 1108-1112 .
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