Role of inflammatory gene polymorphisms in left ventricular dysfunction (LVD) susceptibility in coronary artery disease (CAD) patients
| Autor: | Anshika Srivastava, Balraj Mittal, Naveen Garg, Tulika Mittal, Avshesh Mishra |
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| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty Immunology Coronary Artery Disease Biology Biochemistry Coronary artery disease Ventricular Dysfunction Left INDEL Mutation Polymorphism (computer science) Internal medicine medicine Immunology and Allergy Humans Genetic Predisposition to Disease Myocardial infarction Ventricular remodeling Molecular Biology Genetic Association Studies Demography Inflammation Ejection fraction Polymorphism Genetic Interleukin-6 Tumor Necrosis Factor-alpha Case-control study NF-kappa B p50 Subunit Stroke Volume Hematology Stroke volume Middle Aged medicine.disease Heart failure Case-Control Studies Cardiology Female |
| Zdroj: | Cytokine. 61(3) |
| ISSN: | 1096-0023 |
| Popis: | Rationale Inflammation exacerbates a number of deleterious effects on the heart, most notable being left ventricular dysfunction (LVD). A promoter polymorphism of the NFKB1 gene (encodes p50 subunit) results in lower protein levels of NFkB p50 subunits, which in its dimmer (p50) 2 form has anti-inflammatory effects. The active NFkB transcription factor promotes the expression of over 150 target genes including IL6 and TNF-α . Therefore, the aim of the present study was to assess the association of NFKB1 , IL6 and TNF-α gene polymorphisms with LVD in coronary artery disease (CAD) patients. Methods and Results The present study included a total of 830 subjects (600 CAD patients and 230 controls) and was carried out in two (primary and replication) cohorts. CAD patients with reduced left ventricle ejection fraction (LVEF ⩽45%) were categorized having LVD. The NFKB1 -94 ATTG ins/del (rs28362491), IL6 -174 G/C (rs1800795) and TNF-α -308 G/A (rs1800629) polymorphisms were genotyped by PCR/ARMS-PCR methods. The results of the primary cohort were validated in a replicative cohort and pooled by meta-analysis using Fisher’s and Mantel–Haenszel test. The analysis showed that NFKB1 ATTG 1 /ATTG 1 genotype was significantly associated with LVD (Fisher’s method p -value = 0.007, Mantel–Haenszel OR = 2.34), LV end diastole ( p -value = 0.013), end systole ( p -value = 0.011) dimensions, LV mass ( p -value = 0.024), mean LVEF ( p -value = 0.001) and myocardial infarction ( p -value = 0.043). Conclusion Our data suggests that NFKB1 -94 ATTG ins/del polymorphism plays significant role in conferring susceptibility of LVD and ATTG 1 /ATTG 1 genotype may modulate risk of heart failure by increasing ventricular remodeling and worsening LV function. |
| Databáze: | OpenAIRE |
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