피브리노겐의 수치 및 중요한 아미노산 변형 돌연변이가 뇌중풍에 미치는 영향
Effects of Fibrinogen Level and Genetic Variation in FGA Gene on Korean Stroke Patients
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Backgrounds:Stroke is characterized by loss of brain functions due to a disturbance in the blood vessels supplying blood to the brain, and classified into hemorrhage and ischemia. Stroke is known to be affected by genetic factors and other diseases such as hypertension and cardiovascular diseases. However, the distinctive association between stroke and genetic variations has not discovered yet. Objectives:This study investigated the effects of fibrinogen level and genetic variations in FGA (Fibrinogen alpha chain) gene on stroke in Korean stroke patients and controls. Methods:DNA samples from 674 stroke patients diagnosed by Oriental medical hospitals and 267 controls were used in this study. Two common single nucleotide polymorphism(SNP) with high minor allele frequency(MAF), rs2070011G/A of promoter region and nonsynonymous rs6050A/G of exon 5 in FGA gene, were targeted for Taqman genotyping. Because the TOAST classification is important to the factors and symptoms of stroke, ischemic patients were further classified into five subtypes using diagnosis and clinical data. One-way ANOVA and chi-square test were used for clinical data and genetic association, respectively. Haploview v4.1 program was used for linkage disequilibrium(LD), haplotype and haplotype block analysis. Results:The levels of red blood cells and fibrinogen from clinical data were shown to be significant factors for the sub-groups of TOAST classification. No significant associations of stroke, hemorrhage, ischemic and subtypes of TOAST with rs2070011 and rs6050 of FGA gene were found(P>0.05). However, rs2070011 in promoter region and nonsynonymous rs6050 in exon 5 which produce the amino acid change from threonine to alanine showed a haplotype block and three haplotypes of A-G, G-A, A-A, suggesting that rs2070011 and rs6050 might be co-segregated in generic recombination. Although A-A haplotype of stroke patients showed 64-69% low frequency compared to controls, there was no significant association between stroke and haplotype(P>0.05). Conclusion:This study showed that there was no significant association between stroke and two SNP of rs2070011G/A and nonsynonymous rs6050A/G in FGA gene. However, these two SNP compose a haplotype block and three haplotypes of A-G, G-A, A-A. This finding suggests that rs2070011 and rs6050 are so close as to be positioned as linkage disequilibrium. Nevertheless, no significant association between haplotypes and stroke was found.
Abstract
Backgrounds:Stroke is characterized by loss of brain functions due to a disturbance in the blood vessels supplying blood to the brain, and classified into hemorrhage and ischemia. Stroke is known to be affected by genetic factors and other diseases such as hypertension and cardiovascular diseases. However, the distinctive association between stroke and genetic variations has not discovered yet. Objectives:This study investigated the effects of fibrinogen level and genetic variations in FGA (Fibrinogen alpha chain) gene on stroke in Korean stroke patients and controls. Methods:DNA samples from 674 stroke patients diagnosed by Oriental medical hospitals and 267 controls were used in this study. Two common single nucleotide polymorphism(SNP) with high minor allele frequency(MAF), rs2070011G/A of promoter region and nonsynonymous rs6050A/G of exon 5 in FGA gene, were targeted for Taqman genotyping. Because the TOAST classification is important to the factors and symptoms of stroke, ischemic patients were further classified into five subtypes using diagnosis and clinical data. One-way ANOVA and chi-square test were used for clinical data and genetic association, respectively. Haploview v4.1 program was used for linkage disequilibrium(LD), haplotype and haplotype block analysis. Results:The levels of red blood cells and fibrinogen from clinical data were shown to be significant factors for the sub-groups of TOAST classification. No significant associations of stroke, hemorrhage, ischemic and subtypes of TOAST with rs2070011 and rs6050 of FGA gene were found(P>0.05). However, rs2070011 in promoter region and nonsynonymous rs6050 in exon 5 which produce the amino acid change from threonine to alanine showed a haplotype block and three haplotypes of A-G, G-A, A-A, suggesting that rs2070011 and rs6050 might be co-segregated in generic recombination. Although A-A haplotype of stroke patients showed 64-69% low frequency compared to controls, there was no significant association between stroke and haplotype(P>0.05). Conclusion:This study showed that there was no significant association between stroke and two SNP of rs2070011G/A and nonsynonymous rs6050A/G in FGA gene. However, these two SNP compose a haplotype block and three haplotypes of A-G, G-A, A-A. This finding suggests that rs2070011 and rs6050 are so close as to be positioned as linkage disequilibrium. Nevertheless, no significant association between haplotypes and stroke was found.
참고문헌 (21)
- 황남성, "뇌졸중 중풍은 왜 무서운가", 기계저널, 46(7) (2006)
- 허균, "뇌졸중의 분류와 치료", 노인병, 3(3) (1999)
- Wolf PA, "Secular trends in stroke incidence and mortality : the Framingham Study", Stroke, 23, pp.1551~1555 (1992)
- Welin L, "Analysis of risk factors for stroke in a cohort of men born in 1913", N Engl J Med, 317, pp.521~526 (1987)
- Howard G, "Ethnic differences in stroke mortality between non- Hispanic whites, Hispanic whites, and blacks. The National Longitudinal Mortality Study", Stroke, 25, pp.2120~2125 (1994)
- Reed DM, "The paradox of high risk of stroke in populations with low risk of coronary heart disease", Am J Epidemiol, 131, pp.579~588 (1990)
- Bogousslavsky J, "Risk Factors and Stroke Prevention. European Stroke Initiative(EUSI)", Cerebrovasc Dis, 10(Suppl 3), pp.12~21 (2000)
- Whisnant JP, "Effectiveness versus efficacy of treatment of hypertension for stroke prevention", Neurology, 46, pp.301~307 (1996)
- Lewington S, "Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality : a metaanalysis of individual data for one million adults in 61 prospective studies", Lancet, 360, pp.1903~1913 (2002)
- 권순억, "스타틴 계열 약물의 뇌졸중 예방효과", ~ (2007)
- 개인 유전체의 단일염기다형성 분석을 통한 발병 위험성의 예측, "강창원", Busan science academy, ~, pp.R&E 최종보고서
- Adams RA, "The fibrin-derived gamma 377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease", J Exp Med, 204, pp.571~582 (2007)
- Miller RD, "High-density single-nucleotide polymorphism maps of the human genome", Genomics, 86, pp.117~126 (2005)
- Risch N, "The future of genetic studies of complex human diseases", Science, 273, pp.1516~1517 (1996)
- Barrett JC, "Haploview : analysis and visualization of LD and haplotype maps", Bioinformatics, 21, pp.263~265 (2005)
- Paradowski B, "TOAST classification of Subtypes of Ischaemic Stroke : Diagnostic and Therapeutic Procedures in Stroke", Cerebrovasc Dis, 20, pp.319~324 (2005)
- Carter AM, "Association of the alpha-fibrinogen Thr312Ala polymorphism with poststroke mortality in subjects with atrial fibrillation", Circulation, 99, pp.2423~2426 (1999)
- Standeven KF, "Functional analysis of the fibrinogen Aalpha Thr312Ala polymorphism : effects on fibrin structure and function", Circulation, 107, pp.2326~2330 (2003)
- Wright AF, "Population choice in mapping genes for complex diseases", Nat Genet, 23, pp.397~404 (1999)
- Sachidanandam R, "A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms", Nature, 409, pp.928~933 (2001)
- Kruglyak L, "Variation is the spice of life", Nat Genet, 27, pp.234~236 (2001)