Association of Inflammatory and Oxidative Stress Markers with Metabolic Syndrome in Asian Indians in India

Metabolic syndrome (MetS) is a primary risk factor for cardiovascular disease and is associated with a proinflammatory state. Here, we assessed the contribution of inflammatory and oxidative stress markers towards prediction of MetS. A total of 2316 individuals were recruited in Phase I of the Indian Atherosclerosis Research Study (IARS). Modified ATPIII guidelines were used for classification of subjects with MetS. Among the inflammatory and oxidative stress markers studied, levels of hsCRP (P < .0001), Neopterin (P = .036), and oxLDL (P < .0001) were significantly higher among subjects with MetS. Among the markers we tested, oxLDL stood out as a robust predictor of MetS in the IARS population (OR 4.956 95% CI 2.504–9.810; P < .0001) followed by hsCRP (OR 1.324 95% CI 1.070–1.638; P = .010). In conclusion, oxLDL is a candidate predictor for MetS in the Asian Indian population

Usefulness of C-Reactive Protein as a Marker for Prediction of Future Coronary Events in the Asian Indian Population: Indian Atherosclerosis Research Study

Inflammation plays a pivotal role in all stages of atherosclerosis. Numerous inflammatory, lipid, and cytokines markers have been associated with coronary artery disease (CAD) risk but data directly comparing their predictive value are limited. Studies were carried to elucidate the role of high-sensitivity C-reactive protein (hsCRP), other inflammatory as well as lipid markers and their associations. Among 1021 subjects, comprising 774 CAD affected members from Indian Atherosclerosis Research Study (IARS), plasma hsCRP levels showed strong correlation with inflammatory markers, namely, IL6 (r = .373; P = <.0001), sPLA2 (r = .544; P = <.0001) as also with fibrinogen (r = .579; P = <.0001). Levels of hsCRP were higher among subjects affected by CAD who suffered a repeat coronary event as compared to those who remained event free and subjects in the top quartile of hsCRP (>3.58 mg/L) were found to have a fourfold higher risk. In conclusion, hsCRP appears to be an independent predictor of recurrent CAD events in Asian Indian population

Genetic studies on the APOA1-C3-A5 gene cluster in Asian Indians with premature coronary artery disease

<p>Abstract</p> <p>Background</p> <p>The APOA1-C3-A5 gene cluster plays an important role in the regulation of lipids. Asian Indians have an increased tendency for abnormal lipid levels and high risk of Coronary Artery Disease (CAD). Therefore, the present study aimed to elucidate the relationship of four single nucleotide polymorphisms (SNPs) in the Apo11q cluster, namely the -75G>A, +83C>T SNPs in the APOA1 gene, the Sac1 SNP in the APOC3 gene and the S19W variant in the APOA5 gene to plasma lipids and CAD in 190 affected sibling pairs (ASPs) belonging to Asian Indian families with a strong CAD history.</p> <p>Methods & results</p> <p>Genotyping and lipid assays were carried out using standard protocols. Plasma lipids showed a strong heritability (h²48% – 70%; <it>P </it>< 0.0001). A subset of 77 ASPs with positive sign of Logarithm of Odds (LOD) score showed significant linkage to CAD trait by multi-point analysis (LOD score 7.42, <it>P </it>< 0.001) and to Sac1 (LOD score 4.49) and -75G>A (LOD score 2.77) SNPs by single-point analysis (<it>P </it>< 0.001). There was significant proportion of mean allele sharing (pi) for the Sac1 (pi 0.59), -75G>A (pi 0.56) and +83C>T (pi 0.52) (<it>P </it>< 0.001) SNPs, respectively. QTL analysis showed suggestive evidence of linkage of the Sac1 SNP to Total Cholesterol (TC), High Density Lipoprotein-cholesterol (HDL-C) and Apolipoprotein B (ApoB) with LOD scores of 1.42, 1.72 and 1.19, respectively (<it>P </it>< 0.01). The Sac1 and -75G>A SNPs along with hypertension showed maximized correlations with TC, TG and Apo B by association analysis.</p> <p>Conclusion</p> <p>The APOC3-Sac1 SNP is an important genetic variant that is associated with CAD through its interaction with plasma lipids and other standard risk factors among Asian Indians.</p

Novel network biomarkers profile based coronary artery disease risk stratification in Asian Indians

Background: Multi-marker approaches for risk prediction in coronary artery disease (CAD) have been inconsistent due to biased selection of specific know biomarkers. We have assessed the global proteome of CAD-affected and unaffected subjects, and developed a pathway network model for elucidating the mechanism and risk prediction for CAD. Materials and Methods: A total of 252 samples (112 CAD-affected without family history and 140 true controls) were analyzed by Surface-Enhanced Laser Desorption/Ionization Time of Flight Mass Spectrometry (SELDI-TOF-MS) by using CM10 cationic chips and bioinformatics tools. Results: Out of 36 significant peaks in SELDI-TOF MS, nine peaks could do better discrimination of CAD subjects and controls (area under the curve (AUC) of 0.963) based on the Support Vector Machine (SVM) feature selection method. Of the nine peaks used in the model for discrimination of CAD-affected and unaffected, the m/z corresponding to 22,859 was identified as stress-related protein HSP27 and was shown to be highly associated with CAD (odds ratio of 3.47). The 36 biomarker peaks were identified and a network profile was constructed showing the functional association between different pathways in CAD. Conclusion: Based on our data, proteome profiling with SELDI-TOF MS and SVM feature selection methods can be used for novel network biomarker discovery and risk stratification in CAD. The functional associations of the identified novel biomarkers suggest that they play an important role in the development of disease