| Ischemic stroke (IS) is a class of complex diseases which is caused bymultiple factors, including genetic and environmental factors. The exact etiologyof IS is still not fully clarified, and thus it is difficult to develop effectiveprevention to the disease. Therefore, it is of great value to conduct a study toexamine the etiology of IS. In recent years, the research of etiology of IS hasmade great progress with the development of molecular genetics, molecularbiology and human genomics research, but the exact molecular mechanism isstill not fully elucidated. Molecular epidemiology data shows thatthe genetic susceptibility may play an important role in the pathogenesis ofIS. Besides some special hereditary genes being discovered, the cause of ISmolecular mechanism is still unclean.Nogo gene is a newly discovered neurite growth inhibitory(Neurite growth inhibitor, Nogo), with the function of inhibiting central nervoussystem axonal regeneration and participating in the formation of blood vesselsfiber atheromatous plaque, which is involved in the vascular fibrous plaqueformation. It may play an important role in the occurrence and developmentof IS and other central nervous system diseases. Recently, with the completion of human genome sequencing, studies of single nucleotide polymorphisms (SNP)are becoming the focus of the researchers’ attention. So the researches of SNPscan contribute to explain the relationship between some special sites anddiseases, especially for the susceptibility to complicated diseases, whichprovided some new choices for clinical diagnosis and diseases treatment. Basedon this background, we carried out this study, aiming to examine the frequenciesof allele and genotype distribution of Neurite growth inhibitor-A (Nogo-A) genesingle nucleotide polymorphism (SNP) in Chinese guangxi populations andischemic stroke group, and to compare the distributions of Nogo-Apolymorphism among different races, search the relationship between Nogo-Agene with ischemic stroke and analysize association the genotype of Nogo-Awith Is and the effect of Nogo-A gene polymorphisms on plasma lipid andlipoprotein levels. Meanwhile, we tried to screen susceptibility genes to IS,which would be beneficial for the early prevention and individual therapy.Part1Genetic polymorphisms of Nogo-A gene in Chinese guangxipopulations.Objective: To study the frequencies of allele and genotype distribution ofNeurite growth inhibitor-A (Nogo-A) gene single nucleotide polymorphism(SNP) in Chinese guangxi populations, and to compare the distributions ofNogo-A polymorphism among different races. Methods: The Nogo-A geners12464595C/T, rs2864052G/A, rs17046518G/A, rs2588510C/T and rs887G/A polymorphisms were examined by the polymerase chain reaction-singlebase extension (PCR-SBE) technique and DNA sequencing methods in199guangxi normal individuals. Frequencies of allele and genotype of these Nogo-A gene polymorphisms were analyzed compared with the other four populations(HGP-CEU, HGP-YRI, HGP-JPT and HGP-HCB) from Human Genome Projectgroup (HGP) data.Results: There were Nogo-A gene rs1012603C/T,rs12464595C/T, rs2864052G/A, rs17046518G/A, rs2588510C/T and rs887G/A polymorphisms in Guangxi populations, The Nogo-A gene rs1012603C/T,rs12464595C/T were significant difference between male and female(P<0.05),and Nogo-A gene rs2864052G/A, rs17046518G/A, rs2588510C/T and rs887G/A polymorphisms had no difference between male and female (P0.05). Thefrequencies of allele and genotype distribution of Nogo-A gene rs1012603C/T, rs12464595C/T,rs2864052G/A,rs17046518G/A,rs2588510C/T and rs887G/Apolymorphisms were significant difference compared with HGP-CEU andHGP-YRI populations (P<0.05). The Nogo-A gene rs1012603C/T,rs12464595C/T,rs2864052G/A,rs17046518G/A,rs2588510C/T and rs887G/Apolymorphisms were not significant difference compared with HGP-HCB(P>0.05). When compared with HGP-JPT populations,the frequencies of alleleand genotype distribution of Nogo-A geners1012603C/T and rs12464595C/Tpolymorphism were significant difference (P<0.05). The Nogo-A geners2864052G/A,rs17046518G/A,rs2588510C/T and rs887G/A polymorphismswere not significant difference (P>0.05). These differences among differentethnics might be a influence factor in varied clinical diseases by changing theincidence rate and the form. Conclusion: There were Nogo-A gene rs1012603C/T,rs12464595C/T,rs2864052G/A,rs17046518G/A,rs2588510C/T and rs887G/A polymorphisms in Guangxi populations, and their distributions weresignificantly different among ethnics. It might play an important role foranthropological research. Part2Association of Nogo-A gene single nucleotide polymorphisms withgenetic susceptibility to ischemic strokeObjective: The aim of this study was to examine the frequencies of alleleand genotype distribution of Neurite growth inhibitor-A (Nogo-A) gene singlenucleotide polymorphisms (SNP)，the relationship between Nogo-A gene withischemic stroke (IS) The ssociations of the genotype of Nogo-A with Ischemicstroke and the effect of Nogo-A gene polymorphisms on plasma lipid andlipoprotein levels were also analyzed. Methods: The Nogo-A gene rs12464595C/T,s2864052G/A,rs17046518G/A,rs2588510C/T and rs887G/Apolymorphisms were examined by the polymerase chain reaction-single baseextension (PCR-SBE) technique and DNA sequencing methods in202ISpatients. Frequencies of allele and genotype of these Nogo-A genepolymorphisms were analyzed compared with199normal persons. The plasmalipid and lipoprotein levels were measured by routine method. Results: Therewere Nogo-A gene rs1012603C/T,rs12464595C/T,rs2864052G/A,rs17046518G/A,rs2588510C/T and rs887G/A polymorphisms in control group and ISgroup. The Nogo-A gene rs12464595C/T,rs2864052G/A,rs17046518G/A,rs2588510C/T and rs887G/A polymorphism were not different betweenischemic stroke group and control group(P>0.05). However, the Nogo-Ars1012603C/T polymorphism was significant difference（P<0.05）. The relativerisk suffered from cerebral infarction of T allele was1.513times of the C allele（OR=1.513，95%CI：1.069～2.141）, Plasma Triacylglycerol (TG) and lowdensity lipoprotein-cholesterol (LDL-C) of the patients with ischemic stroke were significantly higher than those of the controls(P<0.05).Conclusion: Therewas an association between Nogo-A gene intron region rs1012603C/Tpolymorphism and IS, and the T allele may be a genetic risk factor of IS.Thepolymorphisms of Nogo-A gene rs12464595C/T,rs2864052G/A,rs17046518G/A,rs2588510C/T and rs887G/A probably were not associated with ischemicstroke. |
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