ABCA1 R219K基因多态性与血脂、脑出血部位及血肿大小的关系
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摘要
目的探讨湖南汉族人群中三磷酸腺苷(ATP)结合盒子转运子A1(ATP-binding cassette transporter 1,ABCA1)R219K基因多态性与血脂、脑出血(cerebral hemorrhage,CH)出血部位及血肿大小的相关性。
方法采用病例对照研究,对280例脑出血(基底节区187例、脑叶56例、脑干24例和小脑13例)和288例非脑卒中对照组进行研究。采用氯仿法抽提外周血白细胞基因组DNA,多聚合酶链式反应(polymerasechain reaction,PCR)和限制性片段长度多态性方法测定ABCA1 R219K基因多态性。
结果全部脑出血组患者和对照组之间ABCA1 R219K基因型和等位基因频率的分布无显著性差异(P＞0.05);将含有变异基因K者合并计算,即变异型携带者R/K+K/K型,脑出血组和对照组之间R/K+K/K基因型的分布频率有显著性差异(P＜0.05);同一部位不同基因型之间的脑出血量在统计学上无显著性差异(P＞0.05)。ABCA1 R219K各基因型之间在血脂水平上无显著性差异(P＞0.05)。脑出血多因素回归方程的主要危险因素包括高血压史、糖尿病史、卒中家族史、吸烟史、空腹血糖高,而变异型携带者R/K+K/K基因型可能为脑出血的独立保护性因素,但P趋于临界值,P=0.047。
结论在本实验中,未发现ABCA1 R219K基因多态性影响血脂;未发现ABCA1 R219K基因多态性与脑出血部位相关;未发现ABCA1R219K基因多态性与脑出血量相关;ABCA1 R219K的变异型携带者R/K+K/K基因型可能是脑出血的独立保护性因素。
Objective To explore the relationship between the ATP-binding cassette transporter A 1(ABCA1) R219K gene polymorphism and the lipids, the location and the size of hematoma in cerebral hemorrhage.
Methods This was a case-controled study, which enrolled 280 cases with cerebral hemorrhage (187 basal ganglia/internal capsule, 56 lobar, 24 brain stem and 13 cerebellum) and 288 healthy controls without CHD and CVD. Polymerase chain reaction-restricted fragments length polymorphism (PCR-RFLP) was used to determine ABCA1 gene polymorphism.
Results The ABCA1 R219K genotype frequencies of healthy controls were R/R33.3%、R/K 48.6% and K/K 18.1%; the ABCA1 R219K genotype distribution in the subjects with cerebral hemorrhage were R/R42.9%、R/K 41.4% and K/K15.7%. There was no significant difference in ABCA1 R219K genotype and allele distribution between all cerebral hemorrhage patients and the healthy controls (P>0.05). Combined the variant gene K together, which was the R/K+K/K genotype, there existed significant difference between cerebral hemorrhage and controls in R/K+K/K genotype (P<0.05). The size of hematoma showed no significant difference among difference genotype in the same location of cerebral hemorrhage frequencies (P>0.05). There was no statistical difference in ABCA1 R219K genotype and allele frequencies between all different locations of recurrent cerebral hemorrhage patients and control group. There was no significant difference in the level of lipids in ABCA1 R219K genotypes (P>0.05). The risk factors of cerebral hemorrhage included the history of hypertension, diabetes, smoking and stroke and high level of fasting blood sugur. The R/K+K/K genotype was possibly the independent protective fator of cerebral hemorrhage, but the P value was 0.047.
Conclusion 1.The ABCA1 R219K genotype polymorphism did not impact the lipids demonstrably; 2.The ABCA1 R219K genotype polymorphism did not impact the locations of cerebral hemorrhage demonstrably; 3.The ABCA1 R219K genotype polymorphism did not impact the size of hematoma in cerebral hemorrhage demonstrably; 4.The variant gene carrier R/K+K/K genotype was possibly the independent protective fator of cerebral hemorrhage.
方法采用病例对照研究,对280例脑出血(基底节区187例、脑叶56例、脑干24例和小脑13例)和288例非脑卒中对照组进行研究。采用氯仿法抽提外周血白细胞基因组DNA,多聚合酶链式反应(polymerasechain reaction,PCR)和限制性片段长度多态性方法测定ABCA1 R219K基因多态性。
结果全部脑出血组患者和对照组之间ABCA1 R219K基因型和等位基因频率的分布无显著性差异(P＞0.05);将含有变异基因K者合并计算,即变异型携带者R/K+K/K型,脑出血组和对照组之间R/K+K/K基因型的分布频率有显著性差异(P＜0.05);同一部位不同基因型之间的脑出血量在统计学上无显著性差异(P＞0.05)。ABCA1 R219K各基因型之间在血脂水平上无显著性差异(P＞0.05)。脑出血多因素回归方程的主要危险因素包括高血压史、糖尿病史、卒中家族史、吸烟史、空腹血糖高,而变异型携带者R/K+K/K基因型可能为脑出血的独立保护性因素,但P趋于临界值,P=0.047。
结论在本实验中,未发现ABCA1 R219K基因多态性影响血脂;未发现ABCA1 R219K基因多态性与脑出血部位相关;未发现ABCA1R219K基因多态性与脑出血量相关;ABCA1 R219K的变异型携带者R/K+K/K基因型可能是脑出血的独立保护性因素。
Objective To explore the relationship between the ATP-binding cassette transporter A 1(ABCA1) R219K gene polymorphism and the lipids, the location and the size of hematoma in cerebral hemorrhage.
Methods This was a case-controled study, which enrolled 280 cases with cerebral hemorrhage (187 basal ganglia/internal capsule, 56 lobar, 24 brain stem and 13 cerebellum) and 288 healthy controls without CHD and CVD. Polymerase chain reaction-restricted fragments length polymorphism (PCR-RFLP) was used to determine ABCA1 gene polymorphism.
Results The ABCA1 R219K genotype frequencies of healthy controls were R/R33.3%、R/K 48.6% and K/K 18.1%; the ABCA1 R219K genotype distribution in the subjects with cerebral hemorrhage were R/R42.9%、R/K 41.4% and K/K15.7%. There was no significant difference in ABCA1 R219K genotype and allele distribution between all cerebral hemorrhage patients and the healthy controls (P>0.05). Combined the variant gene K together, which was the R/K+K/K genotype, there existed significant difference between cerebral hemorrhage and controls in R/K+K/K genotype (P<0.05). The size of hematoma showed no significant difference among difference genotype in the same location of cerebral hemorrhage frequencies (P>0.05). There was no statistical difference in ABCA1 R219K genotype and allele frequencies between all different locations of recurrent cerebral hemorrhage patients and control group. There was no significant difference in the level of lipids in ABCA1 R219K genotypes (P>0.05). The risk factors of cerebral hemorrhage included the history of hypertension, diabetes, smoking and stroke and high level of fasting blood sugur. The R/K+K/K genotype was possibly the independent protective fator of cerebral hemorrhage, but the P value was 0.047.
Conclusion 1.The ABCA1 R219K genotype polymorphism did not impact the lipids demonstrably; 2.The ABCA1 R219K genotype polymorphism did not impact the locations of cerebral hemorrhage demonstrably; 3.The ABCA1 R219K genotype polymorphism did not impact the size of hematoma in cerebral hemorrhage demonstrably; 4.The variant gene carrier R/K+K/K genotype was possibly the independent protective fator of cerebral hemorrhage.
引文
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[2]Santamarina-Fojo S,Peterson K,Knapper C,et al.Complete genomic sequence of the human ABCA1 gene:Analysis of the human and mouse ATP-binding cassette A promoter.Proc Natl Acad Sci USA,2000,97(14):7987-7992
[3]Attie AD,Kastelein JP,Hayden MR.Pivotal role of ABCA1 in reverse cholesterol transport influencing HDL levels and suscep tibility to atherosclerosis.[J]Lipid Res,2001,42:1717-1726
[4]Brooks-Wilson A,MarcilM,Clee S M,et al.Mutations in ABCA1 in Tangier disease and familial high-density lipoprotein deficiency.Nat Genet,1999,22:336-345
[5]Rust S,RosierM,Funke H,et al.Tangier disease is caused by mutations in the gene encoding ATP-Binding cassette Transporter 1.Nat Genet,1999,22:352-355
[6]Koldamova RP,Lefterov IM,Ikonomovic MD,et al.22R-hydroxycholesterol and 9-cis-retinoic acid induce ATP-binding cassette transporter A1 expression and cholesterol effiux in brain cells and decrease amyloid beta secretion.J Biol Chem.2003,278:13244-13256
[7]Sun Y,Yao J,Kim TW,et al.Expression of liver X receptor target genes decreases ellular amyliod beta peptide secretion.J Biol Chem.2003,278:27688-27694
[8]Collins FS,Guyer MS,Charkrabarti A.Variations on a theme:cataloging human DNA sequence variation.[J]Science,1997,278:1580-1581
[9]Clee SM,Zwinderman AH,Engert JC,et al.Common genetic variation in ABCA1 is associated with altered lipoprotein levels and a modified risk for coronary artery disease.Circulation,2001,103:1198-1205
[10]Cenarro A,ArtiedaM,Castillo S,et al.A common variant in the ABCA1 gene is associated with a lower risk for premature coronary heart disease in familial hypercholesterolaemia.[J]Med Genet,2003,40:163-168
[11]Srinivasan SR,Shengxu Li,Wei Chen,et al.R219K polymorphism of the ABCA1gene and its modulation of the variations in serum HDL-C and TG related to age and adiposity in white versus black young adults.Metabolism,2003,52:930-934
[12]Duggirala MK,Cook DA,Mauck KF.Association between atherosclerosis and venous thrombosis.[J]N Eng.J Med.2003,349(4):401-402
[13]Andrikovics H, Pongracz E, Kalina E, et al. Decreased frequencies of ABCA1 polymorphisms R219K and V771M in Hungarian patients with cerebrovascular and cardiovascular diseases. Cerebrovasc Dis, 2006,21(4):254-259
[14]Pasdar A, Yadegarfar G, Cumming A, et al. The effect of ABC A1 gene polymorphisms on ischaemic stroke risk and relationship with lipid profile. BMC Med Genet, 2007, 8:30
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