Association of Tumor necrosis factor G-308 A Polymorphism and Its Correlation with Inflammatory Markers and Lipid Profile in Coronary Heart Disease.

Abstract

C oronary heart disease (CHD) is defined as acute or chronic cardiac disability caused by imbalance between the myocardial supply and demand for oxygenated blood [1]. Cardiovascular disorders (CVD) are the leading cause of morbidity and mortality. CVD will be the most important cause of mortality in India, and CHD will be the single most vital source to this increasing burden of CVD [2]. According to World Health Organization (WHO), CHD is a modern epidemic, not an unavoidable attribute of aging [3]. The burden of CHD is rising in India. In 2008, CHD caused 7.2 million deaths (i.e., 12.8% of total deaths) [4]. In the etiology, CHD is caused by any disease affecting the coronary arteries. More than 90% cases were caused by coronary atherosclerosis and 10% by other causes like vasospasm, Objectives: Tumor necrosis factor-alpha (TNF-α) is a primary proinflammatory cytokine. Single nucleotide polymorphisms present in the promoter region of cytokines have been implicated in the cardiovascular disease pathogenesis. Thus, this study aims to understand the role of permissive promoter variants in TNF-α G-308 A and its correlation with inflammatory markers and lipid profile in the coronary heart disease. Methods: We determined the genotyping of TNF-α G-308 A polymorphism by allele-specific polymerase chain reaction assay in 109 cases with coronary heart disease and 120 controls. Allele and genotype frequencies were estimated. The strength of the association of TNF-α-308 G >A and risk of coronary heart diseases was measured by odds ratios (ORs) and 95% confidence interval. Results: In coronary heart disease and controls, the frequencies of minor allele TNF-α-308 "A" were 0.190 and 0.158, respectively, while the frequencies of major allele TNF-α "G" were 0.809 and 0.841, respectively. The genotype frequencies of TNF-α-308 G-A in coronary heart disease cases were GG=68.81%, GA=26.61%, AA=4.58%; and the frequencies in controls were GG=76.67%, GA=20.83%, AA=2.50%. The OR for wild related to the TNF-α polymorphism was 0.6714 (0.3737-1.206; p=0.233). The OR for heterozygous was 1.387 (0.7468-2.541 p=0.350), and the OR for homozygous was 1.857 (0.4372-8.041 p=0.482). The differences in AA genotype frequencies of TNF-α-308 G-A between cases and controls have led to an OR 1.857; 0.4372-8.041; p=0.4829 in the univariate analysis that was not significant. Conclusion: No association was observed between the permissive promoter variants in the TNF-α gene and an increased risk of coronary heart disease.