Background and Aim Asymmetric dimethylarginine(ADMA),an endogenous inhibitor of nitric oxide synthase(NOS),has been shown to be an independent predictor of coronary heart disease(CHD).Dimethylarginine dimethylaminohyd...Background and Aim Asymmetric dimethylarginine(ADMA),an endogenous inhibitor of nitric oxide synthase(NOS),has been shown to be an independent predictor of coronary heart disease(CHD).Dimethylarginine dimethylaminohydrolase-2(DDAH2) promotes the metabolism of ADMA and plays a key role in formation of the atherosclerosis.We hypothesized that genetic variation inDDAH2 gene might alter the susceptibility to CHD.Methods We tested our hypothesis in a case-control studies.We used ahaplotype-tagging single nucleotide polymorphisms(SNP) approach to identify tag SNP in DDAH2.The SNP were genotyped by poly-merase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and ligase detection reaction(LDR)-sequencing in 1650patients with CHD and 1920 control subjects.Results Apromoter variant-449C/G(rs805305) and -1415G/A(rs2272592)in DDAH2 was identified in the region containing DDAH2.The frequency of those polymorphism were consistent with the lawof Har-dy-Weinberg.The frequency of rs805305 CG +GG or G allele was not significantly different between CHD and wild-type genotype(OR: 0.667,95%CI: 0.374 to 1.187,P>0.05).The frequency of rs2272592 GA +AA or A allele also showed no significant difference between CHD and wild-type genotype(OR: 1.420,95%CI: 0.899 to 2.242,P>0.05).No association was observed be-tween the DDAH2 variant and CHD.These results was independent of age,gender,hypertension,diabetes and hyperlipidemia.Conclusions Our results suggest that although DDAH2/ADMA pathway acts as a critical regulator of coronary atherosclerotic heartdisease,the DDAH2 common variant may not predict the susceptibility to CHD in Chinese population.展开更多
Background: Recent studies indicate a strong functional relevance of the canonical inflammatory interleukin 6 signaling pathway in coronary artery disease (CAD). A genetic association of this signaling pathway with CA...Background: Recent studies indicate a strong functional relevance of the canonical inflammatory interleukin 6 signaling pathway in coronary artery disease (CAD). A genetic association of this signaling pathway with CAD has not been shown yet. We aimed to assess novel single nucleotide polymorphisms (SNPs) from genes of the Interleukin 6 signaling pathway. Results: To identify novel SNPs that are relevant for CAD, we employed a large-scale population-based case-control association study of 2199 cases and 1715 controls and assessed 73 SNPs from 12 genes out of the IL-6 signaling pathway. Results were adjusted to the CAD-related risk factors diabetes, hypertension, Body Mass Index, smoking and sex by logistic regression analysis. In a primary explorative study, we identified 5 SNPs that were significantly associated with CAD (MAPK1_rs6928, MAPK1_rs9340, MAPK1_ rs11913721, MAPK14_rs7757672, JAK1_rs310236). After adjustment to CAD-risk factors, MAPK1_ rs6928 showed the strongest association with CAD (P 0.0217, Odds Ratio 1.36, Confidence Interval 1.05 - 1.77). To reproduce this result, we performed a replication study employing independent patient and control panels. In this study we could not approve the association of rs6928 with CAD. Conclusion: In conclusion, we did not detect significant associations of SNPs from the IL-6 signaling pathway with CAD. Our investigation demonstrates the importance of independent replication studies to verify results from candidate-gene association studies in the quest to discover the underlying pathomechanism of CAD.展开更多
Abnormal levels of plasma lipid have been linked to atherosclerosis, strokes and heart conditions. Variations in high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels are considered as ri...Abnormal levels of plasma lipid have been linked to atherosclerosis, strokes and heart conditions. Variations in high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels are considered as risk factors for coronary artery disease (CAD). Furthermore, triglycerides are a leading cause of cardiovascular disease. Therefore, measurement of plasma lipid levels is an important mortality predictor. Several factors were associated with irregularity in plasma lipids such as genetic alterations. Recent researches have linked single nucleotides polymorphism (SNP) in ApoA5 gene with these deviations. In this study, we reported the effects of the genetic variant c.553G>T in ApoA5 on the levels of plasma lipids. To explore these effects, a case-control study including 280 male and female subjects (44 of them were assigned as CAD cases while the remaining subjects were categorized as control) was established. All patients in the study were recruited from the western region in KSA. The results have detected minor variations in LDL, HDL and cholesterol levels between CAD patients carrying T allele and CAD patients carrying the WT allele. However, there were no significant effects due to these variations. TG levels in the wild type carriers reached up to 291 mg/dl while T allele carriers, the cases, presented lower levels of TG (170 mg/dl and 71 mg/dl). Although, T allele showed no effects on plasma lipids with the exception of TG levels. We suggest by this study that T allele in this SNP might be considered as a valuable tool in the diagnosis of CAD.展开更多
BACKGROUND: The Taq/B, Msp/ and I405V polymorphisms of cholesteryl ester transfer protein (CETP), an important regulatory factor of lipid metabolism, have been attracted much more attention by the researchers. In this...BACKGROUND: The Taq/B, Msp/ and I405V polymorphisms of cholesteryl ester transfer protein (CETP), an important regulatory factor of lipid metabolism, have been attracted much more attention by the researchers. In this study, we investigated the associations between these 3 polymorphisms of CETP gene and variations in plasma lipid and lipoprotein levels in patients with coronary heart disease (CHD). METHODS: Genomic DNA was extracted from leukocytes of 203 CHD patients and 100 control subjects using the salting out method. Genotyping of the CETP gene was performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. Statistical analysis was conducted using the SPSS 10.0 software package. RESULTS: The distribution of allele and genotype frequencies of the Taq/B, MspI, and I405V polymorphisms was similar in the CHD patient group and the control group. The B1B1 genotype of the Taq/B polymorphism was associated with significantly higher TC (P=0.039) and LDL-C (P=0.044) levels than the B2B2 genotype in CHD patients, and with significantly higher LDL-C (P=0.034) levels than the B2B2 genotype in controls. Homozygotes of the I405V polymorphism exhibited significantly higher HDL-C levels than VV homozygotes among control subjects (P=0.023). In male CHD patients with unambiguously assigned haplotypes, B2-M2-V/B2-M2-I patients demonstrated significantly higher HDL-C concentrations than B1-M2-V/B1-M2-I (P=0.023) and B1-M2-V/B1-M2-V patients (P=0.047). CONCLUSIONS: Genetic variations in the CETP gene may account for a significant proportion of the differences in plasma lipid and lipoprotein concentrations among the general population. The B1B1 genotype of the Taq/B polymorphism is probably a genetic risk factor for CHD in the study population.展开更多
The development of premature coronary artery disease(PCAD)is dependent on both genetic predisposition and traditional risk factors.Strategies for unraveling the genetic basis of PCAD have evolved with the advent of mo...The development of premature coronary artery disease(PCAD)is dependent on both genetic predisposition and traditional risk factors.Strategies for unraveling the genetic basis of PCAD have evolved with the advent of modern technologies.Genome-wide association studies(GWASs)have identified a considerable number of common genetic variants that are associated with PCAD.Most of these genetic variants are attributable to lipid and blood pressure-related single-nucleotide polymorphisms(SNPs).The genetic variants that predispose individuals to developing PCAD may depend on race and ethnicity.Some characteristic genetic variants have been identified in Chinese populations.Although translating this genetic knowledge into clinical applications is still challenging,these genetic variants can be used for CAD phenotype identification,genetic prediction and therapy.In this article we will provide a comprehensive review of genetic variants detected by GWASs that are predicted to contribute to the development of PCAD.We will highlight recent findings regarding CAD-related genetic variants in Chinese populations and discuss the potential clinical utility of genetic variants for preventing and managing PCAD.展开更多
文摘Background and Aim Asymmetric dimethylarginine(ADMA),an endogenous inhibitor of nitric oxide synthase(NOS),has been shown to be an independent predictor of coronary heart disease(CHD).Dimethylarginine dimethylaminohydrolase-2(DDAH2) promotes the metabolism of ADMA and plays a key role in formation of the atherosclerosis.We hypothesized that genetic variation inDDAH2 gene might alter the susceptibility to CHD.Methods We tested our hypothesis in a case-control studies.We used ahaplotype-tagging single nucleotide polymorphisms(SNP) approach to identify tag SNP in DDAH2.The SNP were genotyped by poly-merase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and ligase detection reaction(LDR)-sequencing in 1650patients with CHD and 1920 control subjects.Results Apromoter variant-449C/G(rs805305) and -1415G/A(rs2272592)in DDAH2 was identified in the region containing DDAH2.The frequency of those polymorphism were consistent with the lawof Har-dy-Weinberg.The frequency of rs805305 CG +GG or G allele was not significantly different between CHD and wild-type genotype(OR: 0.667,95%CI: 0.374 to 1.187,P>0.05).The frequency of rs2272592 GA +AA or A allele also showed no significant difference between CHD and wild-type genotype(OR: 1.420,95%CI: 0.899 to 2.242,P>0.05).No association was observed be-tween the DDAH2 variant and CHD.These results was independent of age,gender,hypertension,diabetes and hyperlipidemia.Conclusions Our results suggest that although DDAH2/ADMA pathway acts as a critical regulator of coronary atherosclerotic heartdisease,the DDAH2 common variant may not predict the susceptibility to CHD in Chinese population.
基金supported by a research grant of the“Research Center Inflammation Medicine”of the Medical Faculty,Christian-Albrechts-University,University Medical Center Schleswig-Holstein,Campus Kiel,(Arne S.Schaefer)and of the German Ministry of Education and Research through the POPGEN biobank project(01GR0468).
文摘Background: Recent studies indicate a strong functional relevance of the canonical inflammatory interleukin 6 signaling pathway in coronary artery disease (CAD). A genetic association of this signaling pathway with CAD has not been shown yet. We aimed to assess novel single nucleotide polymorphisms (SNPs) from genes of the Interleukin 6 signaling pathway. Results: To identify novel SNPs that are relevant for CAD, we employed a large-scale population-based case-control association study of 2199 cases and 1715 controls and assessed 73 SNPs from 12 genes out of the IL-6 signaling pathway. Results were adjusted to the CAD-related risk factors diabetes, hypertension, Body Mass Index, smoking and sex by logistic regression analysis. In a primary explorative study, we identified 5 SNPs that were significantly associated with CAD (MAPK1_rs6928, MAPK1_rs9340, MAPK1_ rs11913721, MAPK14_rs7757672, JAK1_rs310236). After adjustment to CAD-risk factors, MAPK1_ rs6928 showed the strongest association with CAD (P 0.0217, Odds Ratio 1.36, Confidence Interval 1.05 - 1.77). To reproduce this result, we performed a replication study employing independent patient and control panels. In this study we could not approve the association of rs6928 with CAD. Conclusion: In conclusion, we did not detect significant associations of SNPs from the IL-6 signaling pathway with CAD. Our investigation demonstrates the importance of independent replication studies to verify results from candidate-gene association studies in the quest to discover the underlying pathomechanism of CAD.
文摘Abnormal levels of plasma lipid have been linked to atherosclerosis, strokes and heart conditions. Variations in high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels are considered as risk factors for coronary artery disease (CAD). Furthermore, triglycerides are a leading cause of cardiovascular disease. Therefore, measurement of plasma lipid levels is an important mortality predictor. Several factors were associated with irregularity in plasma lipids such as genetic alterations. Recent researches have linked single nucleotides polymorphism (SNP) in ApoA5 gene with these deviations. In this study, we reported the effects of the genetic variant c.553G>T in ApoA5 on the levels of plasma lipids. To explore these effects, a case-control study including 280 male and female subjects (44 of them were assigned as CAD cases while the remaining subjects were categorized as control) was established. All patients in the study were recruited from the western region in KSA. The results have detected minor variations in LDL, HDL and cholesterol levels between CAD patients carrying T allele and CAD patients carrying the WT allele. However, there were no significant effects due to these variations. TG levels in the wild type carriers reached up to 291 mg/dl while T allele carriers, the cases, presented lower levels of TG (170 mg/dl and 71 mg/dl). Although, T allele showed no effects on plasma lipids with the exception of TG levels. We suggest by this study that T allele in this SNP might be considered as a valuable tool in the diagnosis of CAD.
文摘BACKGROUND: The Taq/B, Msp/ and I405V polymorphisms of cholesteryl ester transfer protein (CETP), an important regulatory factor of lipid metabolism, have been attracted much more attention by the researchers. In this study, we investigated the associations between these 3 polymorphisms of CETP gene and variations in plasma lipid and lipoprotein levels in patients with coronary heart disease (CHD). METHODS: Genomic DNA was extracted from leukocytes of 203 CHD patients and 100 control subjects using the salting out method. Genotyping of the CETP gene was performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. Statistical analysis was conducted using the SPSS 10.0 software package. RESULTS: The distribution of allele and genotype frequencies of the Taq/B, MspI, and I405V polymorphisms was similar in the CHD patient group and the control group. The B1B1 genotype of the Taq/B polymorphism was associated with significantly higher TC (P=0.039) and LDL-C (P=0.044) levels than the B2B2 genotype in CHD patients, and with significantly higher LDL-C (P=0.034) levels than the B2B2 genotype in controls. Homozygotes of the I405V polymorphism exhibited significantly higher HDL-C levels than VV homozygotes among control subjects (P=0.023). In male CHD patients with unambiguously assigned haplotypes, B2-M2-V/B2-M2-I patients demonstrated significantly higher HDL-C concentrations than B1-M2-V/B1-M2-I (P=0.023) and B1-M2-V/B1-M2-V patients (P=0.047). CONCLUSIONS: Genetic variations in the CETP gene may account for a significant proportion of the differences in plasma lipid and lipoprotein concentrations among the general population. The B1B1 genotype of the Taq/B polymorphism is probably a genetic risk factor for CHD in the study population.
基金This work was supported by the National Natural Science Foundation of China(No.81871516,81571841)Open Research Fund of National Clinical Research Center for Geriatric Diseases(No.NCRCG-PLAGH-2018001).
文摘The development of premature coronary artery disease(PCAD)is dependent on both genetic predisposition and traditional risk factors.Strategies for unraveling the genetic basis of PCAD have evolved with the advent of modern technologies.Genome-wide association studies(GWASs)have identified a considerable number of common genetic variants that are associated with PCAD.Most of these genetic variants are attributable to lipid and blood pressure-related single-nucleotide polymorphisms(SNPs).The genetic variants that predispose individuals to developing PCAD may depend on race and ethnicity.Some characteristic genetic variants have been identified in Chinese populations.Although translating this genetic knowledge into clinical applications is still challenging,these genetic variants can be used for CAD phenotype identification,genetic prediction and therapy.In this article we will provide a comprehensive review of genetic variants detected by GWASs that are predicted to contribute to the development of PCAD.We will highlight recent findings regarding CAD-related genetic variants in Chinese populations and discuss the potential clinical utility of genetic variants for preventing and managing PCAD.
