👤 Krushan N Yajnik

Background With the prevalence of coronary artery diseases (CAD) on the rise, especially in the younger population, characterization of non-conventional risk factors remains essential, especially in the inherently predisposed Southeast Asian population. This study aimed at clinical and biochemical profiling in angiographically proven CAD in young Gujarati Indians without conventional risk factors such as tobacco/alcohol consumption. Methodology This single-center, descriptive, cross-sectional case series included consecutive Gujarati patients aged ≤45 years presenting with symptomatic, angiographically significant CAD over a 15-month period. Patients with tobacco or alcohol exposure and those with concomitant pre-existing diabetes mellitus and hypertension were excluded. Clinical characteristics, biochemical parameters (glycated hemoglobin, lipid profile, lipoprotein A (LpA), homocysteine, apolipoproteins), and coronary angiographic findings were recorded. Analyses were primarily descriptive, with limited exploratory comparisons. Results Overall, 2/4 obese patients (50%) and 3/4 obese patients (75%) were newly diagnosed with dysglycemia and dyslipidemia, respectively. Among patients with single-vessel disease (SVD; n = 16), eight (50%) patients presented with ST-segment elevation myocardial infarction, whereas among those with multi-vessel disease (MVD; n = 6), three (50%) patients presented with non-ST-segment elevation myocardial infarction. Elevated low-density lipoprotein cholesterol levels were observed in 8/16 (50%) patients with SVD and 3/6 (50%) patients with MVD. More than 5/6 (83.3%) patients with elevated LpA had SVD. Conclusions The study showed that non-conventional risk factors, such as obesity and family history of CAD, when combined with LpA and lipid profiles, can help in earlier identification of a predisposed individual in a high-risk population. Show less

The APOA5 gene variants, -1131T>C and S19W, are associated with altered triglyceride concentrations in studies of subjects of Caucasian and East Asian descent. There are few studies of these variants in South Asians. We investigated whether the two APOA5 variants also show similar association with various lipid parameters in Indian population as in the UK white subjects. We genotyped 557 Indian adults from Pune, India, and 237 UK white adults for -1131T>C and S19W variants in the APOA5 gene, compared their allelic and genotype frequency and determined their association with fasting serum triglycerides, total cholesterol, HDL and LDL cholesterol levels using univariate general linear analysis. APOC3 SstI polymorphism was also analyzed in 175 Pune Indian subjects for analysis of linkage disequilibrium with the APOA5 variants. The APOA5 -1131C allele was more prevalent in Indians from Pune (Pune Indians) compared to UK white subjects (allele frequency 20% vs. 4%, p = 0.00001), whereas the 19W allele was less prevalent (3% vs. 6% p = 0.0015). Patterns of linkage disequilibrium between the two variants were similar between the two populations and confirmed that they occur on two different haplotypes. In Pune Indians, the presence of -1131C allele and the 19W allele was associated with a 19% and 15% increase respectively in triglyceride concentrations although only -1131C was significant (p = 0.0003). This effect size was similar to that seen in the UK white subjects. Analysis of the APOC3 SstI polymorphism in 175 Pune Indian subjects showed that this variant is not in appreciable linkage disequilibrium with the APOA5 -1131T>C variant (r2 = 0.07). This is the first study to look at the role of APOA5 in Asian Indian subjects that reside in India. The -1131C allele is more prevalent and the 19W allele is less prevalent in Pune Indians compared to UK Caucasians. We confirm that the APOA5 variants are associated with triglyceride levels independent of ethnicity and that this association is similar in magnitude in Asian Indians and Caucasians. The -1131C allele is present in 36% of the Pune Indian population making it a powerful marker for looking at the role of elevated triglycerides in important conditions such as pancreatitis, diabetes and coronary heart disease. Show less

Apolipoprotein AV (ApoAV) gene variant, -1131T>C, is associated with increased triglyceride concentrations in all ethnic groups studied. An MseI based RFLP analysis is the most commonly used method for genotyping this SNP. We genotyped a large cohort comprising 1185 Asian Indians and 173 UK Caucasians for -1131T>C using an ARMS-PCR based tetra-primer method. For quality control, we re-genotyped approximately 10% random samples from this cohort utilizing the MseI RFLP, which showed a 2.9% (3/102) genotyping error rate between the two methods. To investigate further, we sequenced the 900 bp region around the -1131T>C polymorphism in 25 Asian Indians and 15 UK Caucasians and found a number of polymorphisms including the -987C>T polymorphism. Further analysis of the -987C>T SNP showed a higher rare allele frequency of 0.23 in Asian Indians (n = 158) compared to 0.09 in the UK Caucasians (n = 157). This SNP is located 4 bp from the 3' end of the RFLP forward primer and is in weak linkage disequilibrium with -1131T>C variant (r2 = 0.084 and D' = 1). Repeated RFLP analysis of seven subjects heterozygous for -987C>T (seven times), showed discordant results with the sequence at -1131T>C SNP nearly one third (15/49) of the time. We conclude that presence of -987C>T polymorphism in the forward primer of the MseI RFLP assay may lead to allelic drop-out and generate unforeseen errors in genotyping the -1131T>C polymorphism. Our results also emphasise the need for careful quality control in all molecular genetic studies, particularly while transferring genotyping methods between various ethnic groups. Show less