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Correlation Of Human CFH Gene Rs1061170polymorphism With The Coronary Heart Disease

Posted on:2013-04-20Degree:MasterType:Thesis
Country:ChinaCandidate:J ZhouFull Text:PDF
GTID:2234330374978566Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Background and ObjectiveCoronary atherosclerotic heart disease (CHD) is a polygenic disease, the interaction ofgenetic and environmental risk factors of major cardiovascular disease and the leading cause ofdeath. The pathological basis of CHD is atherosclerosis (AS), which itself is a chronicinflammation of the arterial wall process and results. Inflammation, innate immunity andgenetic factors play an important role in the pathophysiology of AS disease. The complementsystem is an important component of the immune system, one of the key factors that generateand maintain the inflammatory response of the arterial intima, broad participation in the body’smicrobial defense response and immune regulation can also be mediated the conductivityimmune pathological injury. Among them, the complement system and complement factor H(CFH) gene and its encoded protein as well as AS related diseases have become a hot researchfrom the perspective of molecular biology in recent years.In the vunerable plaque and rupture of plaques of AS, a large number of complements areactivated. As an important regulatory protein in serum, CFH plays a regulatory role in theactivation of the alternative pathway and anti-inflammatory activity by inhibiting thealternative pathway C3conversion the alternative pathway of the enzyme assembly regulation,which control the further activation of the complement system. CFHrs1061170loci for the1277position of the mutation caused amino acid sequence changes (CFHY402H), histidinereplaces tyrosine amino acid sequence changes will affect CFH affinity to C3b, CFHinactivated and anti-inflammatory effects reduce the impact of the role of its anti-arteryatherosclerosis. Foreign studies have shown that the CFH gene polymorphism is related withCHD. This study is aimed to explore the clinical metabolic parameters between the CFH genepolymorphism and CHD and compare different genotype subgroups by quantitative PCR(realtime fluores-cence quantitative PCR, RTFQ PCR) analysis of the CFH genotypefrequencies distribution. Subject and methods1. Subject and group After screening for patients hospitalized with heart medicine inthe hospital from October2008to June2009,243cases of the Han population in Chongqingagreed to join this study and underwent coronary angiography (CAG) Diagnosis issued byWHO in1979are in line with the diagnostic criteria of ischemic cardiomyopathy (thebackbone of the left coronary artery, left anterior descending artery, left circumflex artery andright coronary artery and its major branches in at least one coronary artery>50%forsignificance of lesions).175cases (male107cases are grouped according to the diagnosisconfirmed by CAG: CHD group,68cases of women)average age of64.65±10.89years old;control group of68cases (male32cases,36cases of women) average age of57.59±11.63years old.2. Methods All of the subjects are Han population in Chongqing, the clinical data arecollected as follows: name, age, sex, blood pressure, height, weight (kg), body mass (BMI)=weight/height2(kg/m2), the family history of cardiovascular disease, alcohol consumption,smoking history, physical activity and eating habits. Stroke, inflammation, rheumatic diseases,liver and kidney dysfunction, cancer and the recent history of infection are excluded.Met the inclusion criteria were fasting3ml venous blood line laboratory tests: blood ureanitrogen blood urea nitrogen (BUN), creatinine (Cr), uric acid (UA), high density lipoproteincholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (APO-B),triglycerides (TG), total cholesterol (TC), detected in the automatic analyzer, fasting plasmaglucose (FBG), fasting insulin (FIN), insulin resistance index (IRI).(IRI=(FIN×FBG/22.5according to the HOMA the Model calculation).Statistical analysis are made by SPSS15.0for Windows software, statistical data entryExcel database, calculation of coronary heart disease and the control group Hardy-Weinberg,(Hardy-Weiyinbeige, Theorem balanced), the measurement data is presented as x±s, thesingle factor to take the analysis of variance and the χ2test, correlation analysis using Pearsoncorrelation analysis. P<0.05is regarded as statictically significant. The statistical analysis ofthe basic clinical data differences between the comparison of coronary heart disease and controlgroups, analysis of the CFH gene rs1061170single nucleotide polymorphisms (the singlenucleotide polymorphism, SNP), gene frequency distribution and CFH genotype frequencydistribution between the various biochemical indicators of the distribution of differences. Results1. Comparison of clinical data, CHD group selected objects are in line with the WHOdiagnostic criteria, coronary heart disease group and control group, two of IRI, the Apo-B(g/l), the TC (mmol/l), BUN (mmol/l), abdominal no significant difference incircumference (cm) gender, coronary heart disease in age, history of hypertension, smokinghistory, triglyceride (TG), total cholesterol (TC), LDL-C were significantly higher, whileHDL-C concentrations were lower than the control group (P<0.05).2. Randomly selected40cases have extracted DNA samples (including coronary heartdisease group and control group) CFHrs1061170loci by direct sequencing results for twodifferent CFH genotype sequencing results were37cases of the homozygous (TT genotype),heterozygous (TC)3case.3. Quantitative PCR between the two groups, the CHD group CFH gene rs1061107in theTT, the TC, the CC genotype frequencies were87.4%,12.6%, and the control group CFHgene rs1061107in94.1%,5.9%,0. The distribution of the two sets of genotype frequencies,no significant (x~2=2.293, OR=2.301,95%CI as0.762-6.943, P>0.05); T allele frequencyof coronary heart disease and control groups were85.3%,97.05%two sets of allele frequencydistribution has no significant difference (X2=2.164, OR=2.213,95%CI=0.748-6.546,P>0.05).4. Clinical metabolic parameters between the two groups and found that the TC genes inthe population in the CHD group, the SBP and DBP, BUN, and Cr was significantly higherthan the TT gene population (P<0.05).Conclusions1. CFH gene rs1061170polymorphism and the Chongqing region part of the Hanpopulation of coronary heart disease has no association.2. TC gene population of1061170CFHrs gene carrying CHD group systolic bloodpressure (systolic blood pressure SBP), diastolic blood pressure (diastolic blood pressure andDBP), BUN, and Cr with TT gene groups was statistically significant.
Keywords/Search Tags:atherosclerosis, coronary heart disease, complement factor H, genepolymorphism
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