| ObjectiveBasigin (BSG), also known as CD147/extracellular matrix metalloproteinase-inducer (EMMPRIN), plays important roles in invasion and metastasis of cancer cells, cardiovascular remodeling, inflammatory diseases, and tissue development and differentiation. The aim of this study is to identify BSG single nucleotide polymorphisms (SNPs) in Chinese Han population and to determine the linkage disequilibrium structure of the gene locus.MethodsPeripheral venous blood samples were collected from48unrelated healthy Chinese Han subjects. Sequences at the BSG locus, including the promoter region, all exons and exon-intron boundaries were amplified and sequenced. SNPs in the sequencing were identified by direct peak read, genotype and allele frequencies were calculated by direct gene counting. Hardy-Weinberg equilibrium (HWE) test and linkage disequilibrium (LD) analysis among the SNPs were analyzed.ResultsA total of21SNPs were identified, among which two were novel. Genotype distributions of all SNPs were consistent with HWE. Four haplotype blocks were constructed throughout the gene locus, and9haplotype tag SNPs (htSNPs) were inferred. Distribution of SNPs was in accordance with the neutrality theory in our population.ConclusionWe porformed a first systematic identification of BSG SNPs in the Chinese Han population, and nine htSNPs are identified. Our study provides basis for further genetic association studies for related diseases as well as pharmacogenetics study for drug response in Chinese Han population. AimsMyocardial remodeling is the most important pathogenesis of chronic heart failure. Matrix metalloproteinases (MMPs), a group of zinc-dependent proteolytic enzyme family, can degrade extracellular matrix components zinc-dependent proteolytic enzyme family and is a key molecule involved in ventricular remodeling. BSG (MIM109480), also known as CD147/extracellular matrix metalloproteinase inducer (EMMPRIN), is a member of immunoglobulin superfamily transmembrane glycoprotein. CD147can promote the secretion of MMPs and increase its activity, the expression levels of CD147significantly increased in a variety of cardiovascular diseases and malignant tumors.Our previous study revealed that BSG rs8259genetic polymorphism was significantly associated with the risk of psoriasis in Chinese Han population.Currently, there were no researches about the relationships of BSG genetic polymorphisms and susceptibility to chronic heart failure in the literature yet. This study was designed to clarify the association of BSG genetic polymorphism and genetic susceptibility to chronic congestive heart failure (CHF) in Chinese Han population.MethodsCollection of peripheral blood from770hospitalized patients with chronic heart failure (CHF) and486age-and sex-matched healthy controls and clinical and lab indicators in both groups. Genomic deoxyribonucleic acid (gDNA) samples were extracted from blood samples by using standard phenol/chloroform protocols. All the subjects were genotyped for the4candidate single nucleotide polymorphisms (SNPs) by methods of direct PCR-products sequencing. ResultsThe frequency distribution of genotypic and allelic frequencies of the four candidate SNP were no significant difference in healthy controls and all CHF patients. In our study, when stratified by smoking and hypertension history to evaluate the influence of these factors on the risk of CHF, we found that carier of rs8259T allele exhibited significantly higher risk to CHF as compared to rs8259AA homozygotes (non-smokers:OR=1.357,95%CI:1.011-1.821,P=0.042; non-hypertensive population:OR=1.777,95%CI:1.298-2.433, P<0.001). The difference remained significant after correction of risk factors for CHF (non-smokers:OR=1.82,95%CI:1.011-1.821, P=0.017; non-hypertensive population:OR=1.459,95%CI:1.022-2.082, P=0.037).ConclusionsBSG rs8259T allele increased the risk of CHF in Chinese Han population. AimsChronic heart failure (CHF) is a worldwide and extremely common, potentially pathogenic clinical syndrome; it is the final outcome of heart disease progress. In recent years, more and more researches of the basic and clinical trial, are deepening the understanding and development of the pathogenesis of heart failure. Akt is a serine/threonine protein kinase, also known as protein kinase B, and plays an important role in regulating myocardial cell growth, angiogenesis, glycometabolism and the apoptosis of myocardial cells, etc. Short-term activated Akt can promote the physiologic myocardial hypertrophy, protect myocardial injury, while prolonged activation of Akt will lead to myocardial pathologic hypertrophy and heart failure. Casein kinase2interacting protein1(CKIP-1) were been discoveried in recent years, which is interacted with Akt and inhibited the activity of Akt; stable expression of CKIP-1can lead to deactivation of Akt and inhibition of cell growth. Therefore, CKIP-1expression level or changing its function may play an important role in the development of heart failure. This part of the study was to explore the association between polymorphism in CKIP-1and genetic susceptibility to heart failure in the han Chinese population in changsha and surrounding areas.MethodsA case-control study composed of898proven patients with chronic heart failure and823sex-, age-matched and ethnically matched control participants were enrolled in the study. We recruited all subjects from March2008to March2011. Analysing CKIP-1SNP data and frequency distribution in Chinese people through the Hapmap database; Application of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for genotype CKIP-1-rs2306235(C>G Pro21Ala).X2test and binary logistic regression analysis for comparing genotype distribution in the cases and controls were carried out. ResultsAll SNPs were in Hardy-Weinberg equilibrium. The CC, CG and GG genotype frequencies of CKIP-1SNP rs2306235were81.5%,17.2%,1.35%in cases and82.3%,17.4%and0.278%in controls, respectively.X2test results showed that the rs2306235GG genotype is significantly overrepresented in the CHF patients than the healthy controls (Crude OR=4.92,P=0.023). However, we found that rs2306235GG genotype frequency was significantly higher in patients with hypertension compared with the healthy controls (adjusted OR=5.163,95%CI=1.032-25.838, P=0.046). Besides, when patients were stratified by heart function, we found that rs2306235GG genotype frequency was significantly higher in patients with heart function of grade III/IV (OR=6.262,95%CI=1.32429.619, P=0.0172). But after binary logistic regression analysis adjusted by risk factors of CHF (age, sex, smoking, drinking, hypertension, diabetes and hyperlipidemia), we found no significant P values.ConclusionsThe CKIP-1s2306235GG genotype may be associated with increased risk for chronic congestic heart failure in Chinese Han population in Changsha and surrounding areas. |
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