The Association Study Between Mulitple Cardiovascular Disease's Predisposing Genes' SNPs, Blood Pressure And Plasma Lipids In Chinese Han Population

Essential hypertension (EHT) and hyperlipemia (HL) are among most important risk factors of multiple kinds of heart and cerebrovacular diseases, such as coronary atherosclerotic heart disease (CHD) and stroke. Now, it is a general viewpoint that cardiovascular diseases, such as EHT, and CHD, are diseases influenced by multiple factors, including complex interactions among multiple genes, environmental and lifestyle factors. Various combinations with different SNPs confer population different susceptibility to cardiovascular diseases, and make the clinic manifestation change, therapeutic efficacy vary in different populations. So, the single nucleotides polymorphisms(SNPs)study of candidate genes of cardiovascular diseases is a hot spot in the research of cardiovascular diseases research. The discovery of predisposing genes study will promise not only to revolutionize the process of disease detection, the practice of preventative and curative medicine, but also to allow researches to better evaluate the roles of non-genetic factors, such as behavior, diet, lifestyle, and physical activity, have on EHT and HL.Today, there are many detection methods for SNPs, such as restriction fragment length polymorphism, DNA sequencing and gene array. The technology of gene array have the high-flux characteristic compared with other methods, therefore it has the advantage in the gene mechanism research for diseases influenced by multiple genes. Our study plans to investigate the allele frequencies of 17 SNPs relative to cardiovascular disease predisposing genes in Chinese Han population, and the association between them and blood pressure and plasma lipoprotein on the basement of verification test for gene array.PARTâ… THE VERIFICATION TESTS FOR GENE ARRAYObjective To evaluate the value of Baio gene array in detecting 17 SNPs relative to cardiovascular disease predisposing genes. Methods Baio gene array chip, PCR and restricted enzyme electrophoresis technique were applied to detected three SNPs (ACE^alu, ApoC3³¹⁷⁵ and ApoC3³²⁰⁶) in 24 blood samples, the DNA sequencing technology was used as the"gold standard". Results About ApoC3³¹⁷⁵ and ApoC3³²⁰⁶: The rate of accuracy of gene array was 97.8% (47/48), and PCR-restricted enzyme electrophoresis technique was 83.3% (20/24); About ACE^alu: the concordance of gene array technology and PCR was close to 80%; the reproducibility of gene array technology was good. Conclusions This kind of gene array chip has a good accuracy, and was faster,simpler and cheaper than DNA sequencing and PCR-restricted enzyme electrophoresis technique,so it has some value in the research of gene mechanism of diseases affected by multiple factors.PARTâ…¡THE INVESTIGATION OF 17 CARDIOVASCULAR DISEASES PREDISPOSING GENE SNPs IN CHINESE HAN POPULATIONObjective To analyze allele frequencies of 17 single nucleotide polymorphisms (SNPs) of 13 cardiovascular disease's predisposing genes in Han. Methods The 17 SNPs genotypes of 60 Han persons whose native places were almost over the mainland of China were detected and analyzed with Baio chip. Results The 3 SNPs allele frequencies which have not been reported in Chinese were: NPRC^-55A allele frequency was 27%,C was 73%;CYP46^rs754203 C allele frequency was 69%,T was 31%, respectively;KCNQ1¹⁴⁰ just was found SS genotype。There were 8 SNPs (ANP²²³⁸, ApoB^Xalâ… , ApoB^Ecorâ… , ACE^Alu, NOS3²⁹⁸, ApoC3³¹⁷⁵, ApoC3³²⁰⁶ and SerpinsA3^rs4934) which allele frequencies in our research were similar to the Han's frequencies (CHB or /and SA0005810) reported in www.hapmap.org and alfred.med.yale.edu; the allele frequencies of AGT²³⁵, ApoB^MspI, ApoE¹⁵⁸, ApoE¹¹²and MTHFR⁶⁶⁷ had significant difference among Shen (present study), CHB and SA0005810 (P<0.05); the difference of ApoB^MspI+/-,ApoB^XbaI-/+,CYP46A1^rs754203C/T and SerpinA3^rs4934C/T in male and female had statistical significance (P<0.05). Conclusions The distributions of these SNPs'allele frequencies are different among different regions, and between male and female. KCNQ1140G is a mutation in Han nationality,so it is probably not play an important role in cardiovascular diseases in Han.PARTâ…¢THE ASSOCIATION STUDY OF CARDIOVASCÎœLAR DISEASE'S PREDISPOSING GENE SNPs AND BLOOD PRESSURE GENE SNPs IN CHINESE HAN POPULATION1 THE VARIANCE ANALYSIS AND MULTIPLE LINEAR REGRESSION ANALYSIS FOR 16 CARDIOVASCÎœLAR DISEASE'S PREDISPOSING GENE SNPs AND BLOOD PRESSURE IN HAN'S MENObjective To learn the association between 16 SNPs in 12 cardiovascular disease predisposing genes and blood pressure of Han men. Methods The 16 SNPs genotypes of 375 Han male whose native places were almost over the mainland of China were detected and analysized with BaiO gene chip. The relationships between the SNPs and blood pressure were analyzed with variance analysis and multiple linear regression analysis. Results Variance analysis and/or multiple linear regression showed that: systolic blood pressure (SBP) was increasing with the elevation of year, AGT²³⁵M, ApoB^Xal+, ApoE^112,158E4 and SerpinA3^rs4934A were relative to the increase of SBP; AGT²³⁵M, NOS3²⁹⁸D, ET-2⁹⁸⁵G, ApoC3³²⁰⁶T and ApoE^112,158E4 maybe had some relation with diastolic blood pressure (DBP) elevation;AGT²³⁵M and ApoB^XalI + were associated with the increase of (SBP-DBP). Conclusions In Han men, AGT²³⁵, NOS3²⁹⁸ and ET-2⁹⁸⁵, ApoB^Xalâ… ,ApoC3³²⁰⁶, ApoE^112,158, SerpinA3^rs4934 might influence the blood pressure.2 THE CASE-CONTROL RESEACH FOR 16 CARDIOVASCÎœLAR DISEASE'S PREDISPOSING GENE SNPs AND EHT GENE SNPs IN CHINESE HAN POPULATIONObjective To investigate the distribution of 6 EHT candidate genotypes and haplotypes, and to analyze their association with essential hypertension. Methods The genotypes and hapotypes in 140 EHT patients and 400 healthy controls in Han population were detected and analyzed with gene array technology and the haplotye analysis software PHASE V 2.1. Results The differences between EHT patients and healthy control about AGT²³⁵M/T, ApoB^Xalâ…  and ACEAlu I/D allele gene frequencies had the statistical significance (P<0.05). The frequency of MIEG+-C3CC in EHT patients was statistical different from healthy controls. Conclusions AGT²³⁵M/T, ApoB^Xalâ…  and ACE^AluI/D could contribute to the onset and progression of EHT.PARTâ…£THE ASSOCIATION STUDY OF CARDIOVASCÎœLAR DISEASE PREDISPOSING GENE SNPs AND PLASMA LIPOPROTEIN GENE SNPs IN CHINESE HAN POPULATION1 THE VARIANCE ANALYSIS AND MÎœLTIPLE LINEAR REGRESSION ANALYSIS FOR 16 CARDIOVASCÎœLAR DISEASE PREDISPOSING GENE SNPs AND PLASMA LIPOPROTEIN IN HAN'S MENObjective To learn the association between 16 SNPs of 12 cardiovascular disease predisposing genes and the levels of blood TC, TG, LDL and HDL in men of Han. Methods The 16 SNPs genotypes of 375 Han male whose native places were almost over the mainland of China were detected. The relationships between the SNPs and blood TC, TG, LDL and HDL were analyzed with variance analysis and multiple linear regression analysis. Results Variance analysis and/or multiple linear regression showed that: ANP²²³⁸C,NPRC^-55C,ApoB^Ecorâ… +,ApoC3³²⁰⁶, ApoE^112,158E3E4 and Serpina3^rs4943 AG were associated with the elevation of TC; ApoC3³²⁰⁶T and MTHFR⁶⁷⁷C might be relationship with TG elevation;ANP²²³⁸C,ET-2⁹⁸⁵G and ApoE^112,158E3E4 might make the level of blood LDL increase. ET-2⁹⁸⁵ A could increase the value of HDL. Conclusions In Han's men, ANP²²³⁸, NPRC^-55, ET-2⁹⁸⁵, ApoB^Ecorâ… , ApoC3³¹⁷⁵, ApoC3³²⁰⁶, ApoE^112,158, MTHFR⁶⁷⁷ and SerpinA3^rs4934 could influence the regulation of plasma lipoprotein.2 THE MULTIPLE LINEAR REGRESSION ANALYSIS FOR 16 CARDIOVASCULAR DISEASE'S PREDISPOSING GENE SNPs AND PLASMA LIPOPROTEIN IN THE AGEDObjective To explore the potential gene factors which affect the level of plasma lipoprotein in the aged. Methods The genotypes of the aged group (90 persons,≥60 years) and control group (408 persons,≤59 years) were tested by Baio chip. The relationships between the SNPs and blood TC, TG, LDL and HDL were analyzed with multiple linear regression analysis. Results In the aged group, the levels of plasma TC, LDL and HDL were less than the controls. The multiple linear regression showed that ApoC3³¹⁷⁵G and ApoE^112,158 E3 could make the increase of TC; NPRC^-55A and ApoE^112,158E3 were associated with the increase of LDL; NOS3²⁹⁸ED was relative to the elevation of HDL. Conclusions ApoC3³¹⁷⁵,ApoE^112,158,NPRC^-55 and NOS3²⁹⁸ might the gene factors of hyperlipemia in Han aged.