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The Study of Relationship between SNPs in Genes Associated with VLDL/LDL Metabolic Pathway and Cerebral Hemorrhage in Han Population of Changsha Area

Author: LiuBaoQiong
Tutor: YangQiDong
School: Central South University
Course: Neurology
Keywords: Cerebral hemorrhage Single nucleotide polymorphisms Transmission disequilibrium test Apolipoprotein A Ⅰ-C Ⅲ-A Ⅳ Apolipoprotein B Lipoprotein lipase Low - density lipoprotein receptor Human subtilisin- converting enzyme
CLC: R743.3
Type: PhD thesis
Year: 2009
Downloads: 153
Quote: 3
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Abstract


Background and Purpose: cerebrovascular disease is recognized worldwide as one of the cause of death of the three major diseases today, cerebral hemorrhage (Cerebral hemorrhage, CH), of which 10 to 55%, the mortality and morbidity, serious harm to human health. Complex pathological mechanisms of cerebral hemorrhage. , Cerebral hemorrhage due to multiple susceptibility gene single nucleotide polymorphisms (single nucleotidespolymorphisms, SNPs) the minor role cumulative, and environmental factors and the incidence. The study will help to elucidate the genetic nature of cerebral hemorrhage of cerebral hemorrhage candidate gene SNPs and susceptibility to cerebral hemorrhage in patients with early detection and prevention to provide a solid theoretical basis and practical guidance. Atherosclerosis risk factors for cerebral hemorrhage. And very low density lipoprotein of (Very lowdensity lipoprotein, VLDL) and LDL (low density lipoprotein, LDL) is currently recognized as an important Rev. atherosclerotic factors, loss adjustment within the endogenous VLDL / LDL metabolic pathways, and may cause VLDL / LDL levels and atherosclerosis, increasing the risk of cerebral hemorrhage. So far, the VLDL / LDL metabolic pathways related to the relationship between gene and cerebral hemorrhage at home and abroad is rarely reported. This study aims to explore the ways set out lipoprotein A Ⅰ-C Ⅲ-A Ⅳ (Apolipoprotein A Ⅰ-C Ⅳ Ⅲ-A, ApoA Ⅰ-C Ⅲ-A Ⅳ), contained lipoprotein B (Apolipoprotein B, ApoB), lipoprotein lipase (Lipoprotein lipase, LPL ), low-density lipoprotein receptor (Low density lipoprotein receptor, LDLR), human subtilisin-converting enzyme (proprotein convertase subtilisin / kexin type 9 PCSK9) gene in Changsha Han population brain hemorrhage. Methods: Subjects from Changsha Han population, including: (1) there is familial aggregation phenomenon cerebral hemorrhage home system group (cerebral Hemorrhage with family history, CHFH): a total of 38 families, including 200 cases of family members, is divided into the following sub-groups : 1 family group of patients with cerebral hemorrhage group: 61 patients, 34 males and 27 females, mean age 53.26 ± 10.60 years old. ② I degree relatives group: 95 cases, 50 males and 45 females, mean age 51.15 ± 14.45 years old. ③ class II kinship group: 23 cases, 9 males and 14 females, mean age 36.82 ± 18.68 years old. ④ Health unrelated relatives: A total of 21 patients, 12 males and 9 females, mean age 52.32 ± 12.74 years old, from the pedigree proband unrelated family members of probands and their Ⅰ, Ⅱ degree relatives spouse. Sporadic cerebral hemorrhage (the sporadic cerebralhemorrhage SCH) Group: 273 cases, male 138 cases, female 135 cases, with an average age of 55.38 ± 12.08 years old. 3 normal control (control) group: 140 cases, male 74 cases, female 66 cases, average age 53.62 ± 13.28 years old. Detection of blood lipids: enzymatic measurement of triglyceride (the Triglyceride TG), total cholesterol (Total cholesterol, TC); determination of high-density lipoprotein (the High densitylipoprotein, HDL) with a precipitating agent to precipitate, and then oxidase supernatant cholesterol; low-density lipoprotein cholesterol (low density lipoprotein, LDL) by Friedwald formulas: LDL = (CHO-HDL)-TG / 5. Genotyping: the use of multiple single-base extension technology and DNA sequencing to detect all objects VLDL / LDL metabolic pathways 5 gene 12 SNPs loci polymorphism combined confirm each other, including: the apoAI-C III-A-IV gene rs12721026, rs2854116, rs45487004, rs670, ApoB gene rs1367117, rs11279109, the LPL gene rs320, LDLR gene rs2569542, rs688, rs5925, PCSK9 gene rs11206510, rs505151. Statistics: using SPSS software sporadic cerebral hemorrhage with normal control group for statistical analysis, the difference between the two groups of genotypes and allele frequencies with x to test different genotype subgroups lipids compared using ANOVA analysis of variance. Using FBAT Software familial aggregation of the phenomenon cerebral hemorrhage family of polymorphic loci built haplotype transmission disequilibrium test (Transmission disequilibrium test, TDT). Results: 1 Changsha Han population exists the apoAI-C III-A-IV gene rs12721026, rs2854116, rs45487004, rs670 polymorphism. ② sporadic cerebral hemorrhage group apoAI-C III-A-IV gene rs12721026, rs2854116, rs45487004, rs670 polymorphism genotypes and allele frequencies with the control group, the difference was not statistically significant (P gt; 0.05) ③ TDT analysis found no the apoAI-C III-A-IV gene rs2854116, rs45487004, rs670 polymorphism allele transmission disequilibrium (P gt; 0.05). ④ rs12721026, rs2854116, rs45487004, rs670 constitute haplotype TDT analysis did not find a single specific haplotype presence of excessive transport phenomena (P gt; 0.05). (5) Sporadic cerebral hemorrhage group and control group rs12721026 polymorphism TT genotype subgroup HDL levels were significantly higher than the GT / GG genotype subgroups (P lt; 0.05), the rs670 polymorphism AA genotype subgroup HDL level was significantly higher GG, GA genotype subgroups (P lt; 0.05). ① Changsha Han population apoB gene rs1367117, rs11279109 polymorphism. ② sporadic cerebral hemorrhage group apoB gene rs1367117, rs11279109 polymorphism genotypes and allele frequency distribution with the control group, the difference was not statistically significant (P gt; 0.05). ⑧ TDT analysis did not find the apoB gene rs1367117 the rs11279109 polymorphism loci allele transmission disequilibrium (P GT; 0.05). (4) of rs1367117, rs11279109 haplotype TDT analysis did not find a single specific haplotype excessive transport phenomena (P gt; 0.05) exists. The ⑤ sporadic cerebral hemorrhage group and the control group rs11279109 polymorphism DD / DI genotype subgroup of TC levels were significantly higher than genotype II subgroup (P lt; 0.05), the rs1367117 polymorphism Ga control group / AA genotype subgroups TC levels were significantly higher than the GG genotype subgroups (P lt; 0.05). (1) Changsha Han population exists the LPL gene rs320 sites polymorphism. ② of sporadic cerebral hemorrhage group and the control group the LPL gene rs320 sites genotype distribution were significantly different (x 2 = 6.95, p = 0.031) a sporadic cerebral hemorrhage group T allele frequency was significantly higher ( x ~ 2 = 5.05, p = 0.025). (3) TDT results displayed the LPL gene rs320T allele transmission significantly increased (Z = 2.144, P = 0.034). ④ sporadic cerebral hemorrhage group rs320 point TT / GT genotype subgroups of TG levels were significantly higher than the GG genotype subgroups (P lt; 0.05) ① Changsha Han population LDLR gene rs2569542, rs688, rs5925 polymorphism. ② LDLR gene rs2569542, rs688, rs5925 polymorphism genotypes and allele frequency distribution and control group difference was not statistically significant (P gt; 0.05) ③ TDT analysis did not find the LDLR gene rs2569542, rs688, rs5925 polymorphism loci allele transmission disequilibrium (P gt; 0.05) ④ The rs2569542, rs688, rs5925 constitute the haplotype TDT analysis did not find a single specific haplotype excessive transport phenomena (P gt; 0.05) exists. ⑤ sporadic cerebral hemorrhage group and the control group LDLR gene rs2569542, rs688, the rs5925 locus genotype TG, TC, HDL and LDL level was no significant difference (P gt; 0.05) 1 Changsha Han population exists PCSK9 gene rs11206510, rs505151 polymorphism. ② sporadic cerebral hemorrhage group PCSK9 gene rs11206510 sites CC / CT genotype and C allele frequency was significantly higher than that in the control group (x to 2 = 4.19, p = 0.041; x to 2 = 4.28, p = 0.039). Sporadic cerebral hemorrhage group rs505151 genotype and allele frequency distribution and the control group, the difference was not statistically significant (P gt; 0.05) The ③ sporadic cerebral hemorrhage group and the control group rs505151 polymorphism GA / GG genotype subgroups LDL levels were significantly higher than the AA genotype subgroup (P lt; 0.05). Conclusion: 1.LPL gene rs320 polymorphism T allele PCSK9 gene polymorphism rs11206510 C allele may Changsha Han population brain hemorrhage. A 2.ApoA I-C III-A-IV gene rs12721026, rs2854116, rs45487004, rs670 apoB gene rs1367117, rs11279109, rs2569542 of LDLR gene, rs688, rs5925, PCSK9 gene rs505151 polymorphism may be associated with Changsha Han population brain bleeding unrelated. A 3.ApoA I-C III-A-IV gene rs12721026, rs2854116, rs45487004, rs670 apoB gene rs1367117, rs11279109, rs2569542 of LDLR gene, rs688, rs5925 point constructed haplotypes may be related to Changsha Han population brain bleeding unrelated. A 4.ApoA I-C III-A-IV gene rs670, rs12721026, apoB gene rs11279109, rs1367117, the LPL gene rs320, PCSK9 gene rs505151 polymorphism may be associated with lipid metabolism in Changsha Han population.

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CLC: > Medicine, health > Neurology and psychiatry > Neurology > Cerebrovascular disease > Acute cerebrovascular disease ( stroke)
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