Associations of genetic variation in fibrinogen with γ' fibrinongen level and ischemic stroke in a Chinese Han population
详细信息 查看官网全文
- 英文论文题名：Associations of genetic variation in fibrinogen with γ' fibrinongen level and ischemic stroke in a Chinese Han population
- 论文作者：虞珊珊 ; 张慧 ; 宗明 ; 孙立山 ; 李牛 ; 范列英
- 年：2012
- 作者机构：上海市东方医院医学检验科;
- 会议召开时间：2012-10-12
- 会议录名称：第三届中国临床微生物学大会暨微生物学与免疫学论坛论文汇编
- 语种：英文
- 分类号：R743.3
- 学会代码：WSWZ
- 会议名称：第三届中国临床微生物学大会暨微生物学与免疫学论坛
- 会议地点：中国浙江杭州
- 主办单位：中国微生物学会临床微生物学专业委员会、《医学参考报》微生物学与免疫学频道编委会、宁波大学医学院附属医院
- 学会名称：中国微生物学会临床微生物学专业委员会
- 页数：2
- 文件大小：101k
- 原文格式：O
- 会议级别：全国
摘要
Background:Ischemic stroke(IS),accounting for 87%of the strokes,is the leading causes of morbidity and mortality in China.Studies shows that inflammatory markers such as leukocytes,fibrinogen,C-reactive protein are independent predictors of IS,most of which result from atherosclerotic disease and recognized as chronic low-grade inflammatory disease.Fibrinogen is an acute-phase coagulation factor produced by hepatocytes and is activated by thrombin to form fibrin monomers and polymers.As a disulfide-bonded dimer,each half of the fibrinogen containing1 Aa chain,1 Bpchain,and 1 y chain,which are encoded by the fibrinogen alpha(FGA),fibrinogen beta(FGB) and fibrinogen gamma(FGG) genes,respectively,ychain can be either the more common yA chain or a γ' chain,which is generated by alternative mRNA processing,resulting in replacement of the last four residues of the yA-chain with an anionic 20-amino-acid sequence.During recent years,attention has focused on the role of γ' fibrinogen in cardiovascular diseases(CVD).An elevated γ' level orγ'/total fibrinogen ratio is observed in cardiovascular disease,especially in the acute phase of ischaemic stroke.However,majority of these studies were performed in Caucasian populations,there are no data about γ' fibrinogen and CVD in Chinese population.Aim of the present study was to analyze the association between fibrinogen polymorphism and γ' fibrinongen level and the risk of IS in the Chinese Han population.Methods:The study was designed as case-control study including 250 patients with documented IS and 250 control subjects in a Chinese Han population.Plasma γ' fibrinogen antigen concentration was measured by enzymelinked immunosorbent assay(ELISA) using a modification of the assay.Four putative functional non-synonymous polymorphisms including FGG 9340T>C(rs1049636),FGA 2224G>A(rs2070011),FGB-455G/A(rs1800790) and FGA Thr312Ala(rs6050) were selected for genotyping using PCR-LDR method.Results:γ' fibrinongen concentrations in IS cases were significantly higher(132±100U/dL) than in controls(114±73U/dL).In the single marker analysis,FGA 2224G>A(rs2070011),(FGA) Thr312Ala(rs6050) and FGB-455G/A(rs1800790) were significantly associated with γ' fibrinogen level,and a gene-dose effect was evident with heterozygotes having intermediate values.The effect of FGG 9340T>C(rs1049636) on γ' fibrinogen level was not statistically significant(P=0.084).However,none of these SNP was asscociated with the risk of IS.We observed statistically significant association between haplotypes AGTG(rs2070011 + rs6050 + rs1049636+rs 1800790) and the decrease risk of IS.Conclusion:An independent association of increased γ' fibrinongen level with IS existed in Chinese Han Population.Haplotypes AGTG was significantly associated with γ' fibrinongen level and the decrease risk of IS.These findings indicate that rs2070011,rs6050 and rs1800790 polymorphisms may contribute to the etiology of IS in the Chinese population.
Background:Ischemic stroke(IS),accounting for 87%of the strokes,is the leading causes of morbidity and mortality in China.Studies shows that inflammatory markers such as leukocytes,fibrinogen,C-reactive protein are independent predictors of IS,most of which result from atherosclerotic disease and recognized as chronic low-grade inflammatory disease.Fibrinogen is an acute-phase coagulation factor produced by hepatocytes and is activated by thrombin to form fibrin monomers and polymers.As a disulfide-bonded dimer,each half of the fibrinogen containing1 Aa chain,1 Bpchain,and 1 y chain,which are encoded by the fibrinogen alpha(FGA),fibrinogen beta(FGB) and fibrinogen gamma(FGG) genes,respectively,ychain can be either the more common yA chain or a γ' chain,which is generated by alternative mRNA processing,resulting in replacement of the last four residues of the yA-chain with an anionic 20-amino-acid sequence.During recent years,attention has focused on the role of γ' fibrinogen in cardiovascular diseases(CVD).An elevated γ' level orγ'/total fibrinogen ratio is observed in cardiovascular disease,especially in the acute phase of ischaemic stroke.However,majority of these studies were performed in Caucasian populations,there are no data about γ' fibrinogen and CVD in Chinese population.Aim of the present study was to analyze the association between fibrinogen polymorphism and γ' fibrinongen level and the risk of IS in the Chinese Han population.Methods:The study was designed as case-control study including 250 patients with documented IS and 250 control subjects in a Chinese Han population.Plasma γ' fibrinogen antigen concentration was measured by enzymelinked immunosorbent assay(ELISA) using a modification of the assay.Four putative functional non-synonymous polymorphisms including FGG 9340T>C(rs1049636),FGA 2224G>A(rs2070011),FGB-455G/A(rs1800790) and FGA Thr312Ala(rs6050) were selected for genotyping using PCR-LDR method.Results:γ' fibrinongen concentrations in IS cases were significantly higher(132±100U/dL) than in controls(114±73U/dL).In the single marker analysis,FGA 2224G>A(rs2070011),(FGA) Thr312Ala(rs6050) and FGB-455G/A(rs1800790) were significantly associated with γ' fibrinogen level,and a gene-dose effect was evident with heterozygotes having intermediate values.The effect of FGG 9340T>C(rs1049636) on γ' fibrinogen level was not statistically significant(P=0.084).However,none of these SNP was asscociated with the risk of IS.We observed statistically significant association between haplotypes AGTG(rs2070011 + rs6050 + rs1049636+rs 1800790) and the decrease risk of IS.Conclusion:An independent association of increased γ' fibrinongen level with IS existed in Chinese Han Population.Haplotypes AGTG was significantly associated with γ' fibrinongen level and the decrease risk of IS.These findings indicate that rs2070011,rs6050 and rs1800790 polymorphisms may contribute to the etiology of IS in the Chinese population.
Background:Ischemic stroke(IS),accounting for 87%of the strokes,is the leading causes of morbidity and mortality in China.Studies shows that inflammatory markers such as leukocytes,fibrinogen,C-reactive protein are independent predictors of IS,most of which result from atherosclerotic disease and recognized as chronic low-grade inflammatory disease.Fibrinogen is an acute-phase coagulation factor produced by hepatocytes and is activated by thrombin to form fibrin monomers and polymers.As a disulfide-bonded dimer,each half of the fibrinogen containing1 Aa chain,1 Bpchain,and 1 y chain,which are encoded by the fibrinogen alpha(FGA),fibrinogen beta(FGB) and fibrinogen gamma(FGG) genes,respectively,ychain can be either the more common yA chain or a γ' chain,which is generated by alternative mRNA processing,resulting in replacement of the last four residues of the yA-chain with an anionic 20-amino-acid sequence.During recent years,attention has focused on the role of γ' fibrinogen in cardiovascular diseases(CVD).An elevated γ' level orγ'/total fibrinogen ratio is observed in cardiovascular disease,especially in the acute phase of ischaemic stroke.However,majority of these studies were performed in Caucasian populations,there are no data about γ' fibrinogen and CVD in Chinese population.Aim of the present study was to analyze the association between fibrinogen polymorphism and γ' fibrinongen level and the risk of IS in the Chinese Han population.Methods:The study was designed as case-control study including 250 patients with documented IS and 250 control subjects in a Chinese Han population.Plasma γ' fibrinogen antigen concentration was measured by enzymelinked immunosorbent assay(ELISA) using a modification of the assay.Four putative functional non-synonymous polymorphisms including FGG 9340T>C(rs1049636),FGA 2224G>A(rs2070011),FGB-455G/A(rs1800790) and FGA Thr312Ala(rs6050) were selected for genotyping using PCR-LDR method.Results:γ' fibrinongen concentrations in IS cases were significantly higher(132±100U/dL) than in controls(114±73U/dL).In the single marker analysis,FGA 2224G>A(rs2070011),(FGA) Thr312Ala(rs6050) and FGB-455G/A(rs1800790) were significantly associated with γ' fibrinogen level,and a gene-dose effect was evident with heterozygotes having intermediate values.The effect of FGG 9340T>C(rs1049636) on γ' fibrinogen level was not statistically significant(P=0.084).However,none of these SNP was asscociated with the risk of IS.We observed statistically significant association between haplotypes AGTG(rs2070011 + rs6050 + rs1049636+rs 1800790) and the decrease risk of IS.Conclusion:An independent association of increased γ' fibrinongen level with IS existed in Chinese Han Population.Haplotypes AGTG was significantly associated with γ' fibrinongen level and the decrease risk of IS.These findings indicate that rs2070011,rs6050 and rs1800790 polymorphisms may contribute to the etiology of IS in the Chinese population.
引文