Dataset Information

Hsp70-2 gene polymorphism: susceptibility implication in Tunisian patients with coronary artery disease.

ABSTRACT:

Unlabelled

Coronary artery disease (CAD) is a multifactorial disease where genetic and environmental factors interact in complex ways to cause the disease. Heat shock protein genes are involved in the progress of CAD. This implies that genetic variants of Hsp70-2 genes might contribute to the development of the CAD.

Aim of study

The aim of this study was to characterize statistical correlation of linkage between lipid profiles, polymorphism PstI site of Hsp70-2 gene and CAD.

Patients and methods

This study was carried out on Tunisian patients with CAD recruited from Hospital of Fattouma Bourguiba of Monastir-Tunisia. Polymerase chain reaction and restriction enzymes were used to determine the genotypic distributions in 252 unrelated patients and 151 healthy control subjects. Further, ApoA-I and ApoB as well as the serum total of cholesterol, HDL, triglyceride, and hs-CRP levels were measured.

Results

We showed a decreased level of ApoA-I, whereas the levels of each of ApoB and hs-CRP were increased in patients with CAD compared with control group. In addition our studies of a polymorphic PstI site of Hsp70-2 gene at position 1267 of the Hsp70-2 gene have revealed that the allelic frequency of P2 was significantly more frequent in CAD patients than controls group (p=0.007, OR=1.495). The genotypic distribution showed a high incidence of P2/P2 genotype in CAD patients (0.190) compared to healthy control (0.009) with reach significant difference (p=0.006). The P2 carriers showed a significantly increased of Total-Cholesterol (CT) and C-reactive protein (hs-CRP) levels in CAD patients (p=0.008 and p=0.018, respectively).

Conclusion

The high incidence of P2-Hsp70-2 genotype in CAD patients and the significantly association of P2/P2 genotype with elevated Total Cholesterol and hs-CRP levels, supported that P2-Hsp70-2 genotype has susceptibility implication in CAD and could increased the risk of CAD in Tunisian population.

SUBMITTER: Hrira MY

PROVIDER: S-EPMC3558340 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Publications

Hsp70-2 gene polymorphism: susceptibility implication in Tunisian patients with coronary artery disease.

Hrira Mohamed Yahia MY Chkioua Latifa L Slimani Afef A Chahed Henda H Mosbah Habib H Khaldoun Hamda Ben HB Ferchichi Salima S Addad Faouzi F Miled Abdelhedi A

Diagnostic pathology 20120726 1

<h4>Unlabelled</h4>Coronary artery disease (CAD) is a multifactorial disease where genetic and environmental factors interact in complex ways to cause the disease. Heat shock protein genes are involved in the progress of CAD. This implies that genetic variants of Hsp70-2 genes might contribute to the development of the CAD.<h4>Aim of study</h4>The aim of this study was to characterize statistical correlation of linkage between lipid profiles, polymorphism PstI site of Hsp70-2 gene and CAD.<h4>Pa ...[more]

PMID: 22834788

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Project description:BackgroundData of susceptible gene polymorphisms related to progression of coronary atherosclerosis in patients with three-vessel disease (TVD) is limited in China. This case-control study aimed to analyze the differences of variant carrier frequencies between cases and controls, and to explain the possible genetic effects on the progression of TVD.MethodsA total of 8943 TVD patients were consecutively enrolled. Major adverse cardiac and cerebrovascular events (MACCE) included all-cause death, acute myocardial infarction, repeat revascularization, readmission and stroke. Patients with 1-year MACCE in this cohort were selected as MACCE group. Blood samples from MACCE group and non-CAD control groups were collected, and a deoxyribonucleic acid library was created. A total of 34 tag or hot single nucleotide polymorphisms (SNPs) in six genes including CDKN2B-AS1, ADAMTS7, ABO, ADAMTS13, IL-18, and PECAM1 were analyzed by a SNPscan™ multi-genotyping kit. Carrier frequencies of each SNP were compared between the two groups using dominant, recessive and codominant allele model, respectively. Multivariate logistic regression model was established.ResultsVariant allele frequencies of rs10757274, rs1333042, rs1333049, rs4977574, rs9632884, rs1063192 and rs3217986 on CDKN2B-AS1 gene showed significant differences between the two groups in at least one allele model. Variant allele frequency of rs3217986 was not statistically significant after adjusting for the false discovery rate using Benjamini-Hochberg procedure (Q > 0.05). Variant allele frequencies of rs1333049, rs10757274, rs4977574 on CDKN2B-AS1 gene were significantly higher in MACCE group in all dominant, recessive and codominant models. Rs1055432 on ADAMTS13 and rs8176694 on ABO gene showed threshold significance between the two groups. After multivariable adjustment, G mutant homozygous rs9632884 (GG vs. GC + CC) (OR: 0.24; 95% CI: 0.09-0.65; P = 0.005) on CDKN2B-AS1 gene were independent protective factor of MACCE in recessive model.ConclusionsIn patients with TVD in China, variant alleles on CDKN2B-AS1 gene may form part of the genetic basis of coronary atherosclerosis progression, promoting or suppressing ischemic events.

Project description:Coronary artery disease (CAD) is a disease in which a waxy substance called plaque builds up inside the coronary arteries. Apelin is a novel endogenous peptide with inotropic and vasodilatory properties and is the ligand for the angiotensin receptor-like 1 (APJ) receptor. We aimed to determine genotype and allele frequencies of APJ receptor A445C gene polymorphism in Turkish patients with CAD and healthy controls by RFLP-PCR. This study was performed on 159 unrelated CAD patients and 62 healthy controls. We obtained AA, AC and CC genotype frequencies in CAD patients as 41.5%, 49.1% and 9.4%, respectively. In the control group, frequencies of genotypes were found as 35.5% for AA, 48.4% for AC and 16.1% for CC. We did not observe difference in APJ receptor A445C polymorphism between CAD patients and healthy controls (?(2) = 2.178; df = 2; P = 0.336). The A allele was encountered in 66% (210) of the CAD and 59.7% (74) of the controls. The C allele was seen in 34% (108) of the CAD and 40.3% (50) of the controls. Allele frequencies of interested genes were not significantly different between groups (?(2) = 1.57; df = 1; p = 0.225). The frequencies of APJ receptor A445C genotype were not significantly different between control and patients. None of the three APJ receptor A445C genotypes, AA, AC and CC displayed significant difference in CAD patients. We did not find any difference in the clinical parameters except for weight and diastolic blood pressure levels in the AA, AC and CC genotypes of patients. Individuals with CC genotypes had significantly higher weight, systolic and diastolic blood pressure levels and systolic blood pressure than other genotypes, P ? 0.05. In addition, HDL-C level was found decreased, but this reduction was not statistically significant. Contrarily, the low levels of weight, SBP, DBP and TC were statistically significant in the subjects with AA genotype in CAD. In conclusion, CC genotype carriers may have more risk than other genotypes in the development of hypertension in CAD, but not AAgenotype carriers. We suggest that this polymorphism may not be a marker of CAD, but it may cause useful in function of the apelin/APJ system and may be a genetic predisposing factor for diagnostic processes and can be helpfull in finding new treatment strategies. We think that it is required to further comprehensive studies in order to make clear this situation in CAD.

Project description:ObjectiveBy releasing mediators, like nitric oxide (NO), vascular endothelium is considered so significant in the process of atherosclerotic . In fact, the major functions of NO consist in inhibiting the activation of platelet, relaxing the muscles (vascular and smooth ones), and modulating the growth and the migration of cells (vascular and smooth ones). Therefore, this process makes the endothelial nitric oxide synthase (NOS3) considerably important because it possesses atheroprotective activity. Polymophisms, rs1808593 (10G/T) as well as rs891512 (G24943A) within NOS3 gene, play major role in the coronary artery disease (CAD) development. The aim of the study is to evaluate the relationship between the 10G/T and G24943A polymorphisms and the CAD among Tunisian individuals.MethodsWe included, in this survey, a set of 274 patients suffering from CAD together with 162 normotensive subjects. The PCR-RFLP was applied to analyze the polymorphism of intron 23 (10G/T) gene, while the ASA-PCR was used to analyze the intronic G24943A gene polymorphism. Overall and subgroup analyses were performed. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the association between NOS3 10G/T and G24943A polymorphisms as well as CAD risk. Statistical analysis was performed with SPSS V.10.ResultsThe genotype frequencies for G24943A polymorphism differed significantly between the CAD patients and the controls. The former had a frequency of 11.4% for the AA genotype, 34.7% for the GA genotype and 53.9% for the GG genotype. The latter had a frequency of only 2.5% for the AA genotype, 29.7% for the GA genotype and 67.7% for the GG genotype (χ2=7.62; OR=1.79; p=0.006). The CAD patient group showed a significantly-higher frequency of the A allele compared to the controls (0.28 vs. 0.16; χ2=15.20; p<0.001). The odds ratio of CAD for A vs. G allele frequency was statistically significant 1.99 (1.4-2.82) at 95% CI. The genotype distribution for the 3 investigated variants of 10G/T were not significantly different between CAD and control subjects (χ2=1.46; OR=1.72; p=0.22). Whereas, 10G/T has revealed barely allelic (χ2=4.45; OR=2.3; p=0.034) correlation with coronary artery disease Conclusion: The present study was designed so that there would be an association between the CAD and NOS3 polymorphism (G24943A). However, these results have proven that the polymorphism of 10G/T is not associated with CAD in the Tunisian population.

Dataset Information

Hsp70-2 gene polymorphism: susceptibility implication in Tunisian patients with coronary artery disease.

Unlabelled

Aim of study

Patients and methods

Results

Conclusion

Publications

Hsp70-2 gene polymorphism: susceptibility implication in Tunisian patients with coronary artery disease.

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