Endothelial Nitric Oxide Synthase T-786C and G-894T Gene Polymorphisms: A Risk Assessment of Coronary Heart Disease.

INTRODUCTION: The polymorphism of the endothelial nitric oxide synthase (eNOS) gene is thought to enhance the risk of coronary heart disease (CHD). The most protruding reason for endothelial dysfunction is the diminished production of NO. In the eNOS encoding gene, a number of mutations were associated with decreased NO effect promoting the presence of CHD. AIM: This study aims to look at the role of polymorphisms in the eNOS genes G-894T and T-786C in young South Indians. MATERIALS AND METHODS: From January 2022 to May 2022, 91 angiographically proven CHD subjects attending the Department of Cardiology and Medicine and 91 controls from a master health checkup in the age group of 45 years participated in this observational cross-sectional study at SRM Medical College Hospital and Research Centre in Chennai, Tamil Nadu, India. Overnight fasting plasma samples were taken for analysis of the lipid profile as well as NO by Griess reaction utilizing an enzyme-linked immunosorbent assay (ELISA) technique. Polymerase chain reaction (PCR) and restricted fragment length polymorphism (RFLP) were used to amplify the T-786C and G-894T eNOS genes. RESULTS: When compared to controls, the mean level of serum NO in CHD patients was considerably lower. For eNOS T-786C polymorphism, the distribution of TC genotype (p = 0.017), odds (OD) ratio = 2.1, CC genotype (p = 0.011), OD ratio = 3.75, and minor C allele frequency (p = 0.001). And for eNOS G-894T polymorphism, the distribution of GT genotype (p = 0.01), TT genotype (p =0.02) with OD ratio and minor T allele frequency (p = 0.002) with OD ratio = 1.07 and 0.83. CONCLUSION: Our study concludes that the polymorphism of eNOS T-786C and G-894T genes may be the main causative association for the presence of CHD. How to cite this article: Jaishankar T, Shivasekar M, Vinodhini VM. Endothelial Nitric Oxide Synthase T-786C and G-894T Gene Polymorphisms: A Risk Assessment of Coronary Heart Disease. J Assoc Physicians India 2023;71(9):45-50.

Smoking Induces the Circulating Levels of Matrix Metalloproteinase-9 and Its Association with Cardiovascular Risk in Young Smokers.

Objective: Smoking causes cardiovascular risk, which may alter the stability between the production and degradation of the extracellular matrix. Matrix metalloproteinase-9 (MMP-9) is a zinc-containing endopeptidase that degrades the extracellular matrix and is involved in tissue remodelling and several physiological processes. As a result, smoking-induced elevated serum MMP-9 levels, particularly at a younger age, raise the risk of coronary heart disease (CHD). Thus, this study aimed to determine the possible relationship between smoking-induced circulating MMP-9 and the risk of cardiovascular disease in young smokers. Methods: In this cross-sectional study, the patients were divided into three groups. Each group contains 120 study participants. Group one consisted of 120 healthy individuals with no physical and mental illness, group two consisted of 120 active smokers with a heart disease, and group three consisted of 120 active smokers with a heart disease and diabetes, who attended Sri Ramaswamy Memorial Hospital for cardiology checkup at the age of 20-55 years. The serum MMP-9, high-sensitivity C-reactive protein (hs-CRP), and apolipoprotein-E (APO-E) levels were analyzed using the ELISA method, and the lipid levels were measured enzymatically using AU480 automatic analyzer (Beckman Coulter). Results: Compared with non-smokers, the study shows that the mean serum MMP-9, hs-CRP, and APO-E levels were significantly higher in smokers (p<0.001). A strong relationship was also found between MMP-9 and hs-CRP, APO-E, smoking load, and smoking intensity. Conclusions: A significant association was found between cigarette smoking with MMP-9, and relative exposure to circulating inflammation markers plays a potential role in the pathogenesis of CHD.

Role of Cigarette Smoking on Serum Angiotensin-Converting Enzyme and Its Association With Inflammation and Lipid Peroxidation.

Introduction Cigarette smoking promotes angiotensin-converting enzyme (ACE) production and causes a substantial change in inflammation and oxidative stress, resulting in an increase in antioxidant activity and lipid peroxidation. Objective The study's goal is to determine the role of cigarette smoking on serum ACE and its relation with inflammatory markers and lipid peroxidation. Methods The cross-sectional study consists of three groups. The study participants are all men between the age group of 20 to 55 years. Group 1 includes 120 healthy controls as nonsmokers, Group 2 consists of 120 active smokers with coronary heart disease (CHD) and Group 3 includes 120 active smokers with diabetic CHD patients attending the SRM Medical College Hospital in Tamil Nadu for cardiology and medical Outpatient. Measurements of serum ACE, oxidized low-density lipoprotein (oxLDL), high-sensitivity C-reactive protein (hsCRP), and matrix metalloprotease-9 (MMP-9) were performed using the ELISA method (enzyme-linked immunosorbent assay). Using a spectrophotometric approach, the total antioxidant capacity and lipid peroxidation, particularly Malondialdehyde (MDA), were assessed. Results The mean serum ACE (92.35±10.28), oxLDL (48.59±8.56), hs-CRP (5.87±1.62), MMP-9 (89.20±30.19), and MDA (1.146±0.198) levels were significantly (p-value <0.0001) higher in smokers with CHD and diabetes (group 3) when compared to group 1 and group 2. On the other hand, the total antioxidant capacity (0.413±0.097) of smokers of group 3 was found to be (p<0.0001) significantly lower than those of group 1 and group 2. The study also demonstrated a significant correlation between ACE with MDA, ox-LDL, total antioxidant capacity, hs-CRP, MMP-9, smoking load, and smoking intensity in smokers. Conclusion The study concludes a substantial correlation exists in smokers owing to ACE modification, which results in inflammation and lipid peroxidation activation. This is strongly associated with an increased risk of major cardiovascular events.

Assessment of Remnant Lipoprotein Cholesterol and Oxidized Low density Lipoprotein Associated with Low-grade Inflammation in Coronary Heart Disease Subjects of Young South Indian Population.

BACKGROUND: Coronary heart disease (CHD) is a major disease entity responsible for significant mortality and morbidity in the Indian population. The prevalence of CHD is increasing day by day in India. The hardening of arteries is linked to oxidative variations in low-density lipoproteins (LDLs). Modification of LDL to oxidized LDL (ox-LDL) is a crucial step in the oxidation hypothesis of atherogenesis. Oxidized LDL and remnant lipoprotein cholesterol (RLP-C) stimulate the immune and inflammatory reactions and promote atherosclerosis. Because of its lesser size along with high cholesterol content, and increased residence period in blood the remnant lipoproteins are highly atherogenic. Remnant lipoproteins transport more cholesterol to macrophages compared to LDL particles. Remnant lipoproteins enter into the arterial wall easily and are taken up directly by macrophages. This leads to the formation of foam cells, thus initiating the lipid-laden plaque. High sensitive C-reactive protein acts as a nonspecific inflammatory marker. Oxidized LDL along with RLP-C and high-sensitivity C-reactive protein (hs-CRP) play crucial role in progression of CHD. AIM OF THE STUDY: The aim of the study is to assess ox-LDL and RLP-C associated with hs-CRP as potential biomarkers in the development of CHD. MATERIALS AND METHODS: This cross-sectional study was conducted in Sri Ramaswamy Memorial Medical College Hospital and Research Centre on subjects appearing for master health check-up and medicine. This cross-sectional study was conducted on 273 subjects who were age and sex match in the age group of ≤45 years. 91 Non-Diabetic subjects with CHD, 91 Diabetic subjects with CHD, and 91 normal healthy subjects were selected as control. After overnight fasting, body fluid samples were collected for analysis for lipid profile, ox-LDL, and hs-CRP. Oxidized LDL and hs-CRP were measured by enzyme-linked immunosorbent assay (ELISA) method and lipid profile was measured using Auto Analyser AU480. Statistical analysis was done using Student's t-test and Pearson's correlation analysis for the comparison between two groups. RESULTS: The mean level of ox-LDL, RLP-C, and hs-CRP was significantly elevated in CHD group. A significantly positive correlation was observed between plasma ox-LDL, RLP-C, and hs-CRP. CONCLUSION: These results suggest that the link between high ox-LDL, RLP-C, and hs-CRP levels might be interrelated to atherogenesis in subjects with CHD. In addition to conventional parameters, ox-LDL, RLP-C, and hs-CRP can prove to be a valuable tool in risk assessment of CHD. Journal of the Association of Physicians of India (2022): 10.5005/japi-11001-0009.