Research team in IGIB, led by Dr Shantanu Sengupta, have identified unique DNA methylation patterns that could identify CAD in Indian patients with over 93% accuracy, which might open avenues for biomarker discovery specific to the Indian population.
Aswini B | 06 November 2019
Coronary artery disease (CAD) is a complex disease caused by various factors from genetic to environmental effects. According to WHO, around 56 million deaths were reported worldwide due to CAD between 2000 to 2012. There is an increased incidence of CAD in the past 60 years. It is anticipated that by 2030, 60% of death in India could be of CAD. Genomic studies have provided useful insights into various diseases and helped us in developing better diagnosis and treatment. Similarly, in the case of CAD, genome-wide association (GWAS) studies on patients have identified multiple SNPs in their genome. However, these account for only 10-15% of the disease risk. Alternatively, genome modifications mediated by epigenetic modifiers are also thought to play a major role in the manifestation of CAD. Hence, the focus has been placed on epigenetic modifiers, especially on DNA methylation. DNA methylation is a stable DNA modification and is known to regulate gene expression. Various studies have reported the involvement of altered methylation in cardiovascular diseases.
The research team in IGIB, led by Dr Shantanu Sengupta, have identified signals in 11 genes, from data that consist of 32 samples with 180 methylation positions, through machine learning, that could discriminate CAD patients with over 93% accuracy. "This can be used as a prognosis in finding CAD patients", says the first author of the paper Suboshree Ghose. This might open avenues for biomarker discovery specific to the Indian population.CAD patients are known to have an accumulation of intracellular cholesterol and high triglyceride levels. The team has performed targeted bisulfite sequencing (a technique to identify methylation patterns in DNA) of several genes known to be involved in cholesterol synthesis and metabolism and endothelial dysfunction. From the analysis of the methylation status of genes involved in cholesterol synthesis and metabolism, the authors conclude that there was less synthesis of cholesterol. Cholesterol efflux pathway was also affected leading to low HDL and LDL levels. Ghose says, "LDL may not be an appropriate risk marker for CAD in the Indian population. Various studies have shown that as well". Surprisingly the authors also found low triglyceride levels in the patients. This might be because of various reasons like B12 deficiency or dietary pattern or simply a population effect.
Incidence of CAD in Indian patients is almost a decade earlier than in western countries. The reason could be a different methylation profile of Indian population due to its unique dietary habits. It is interesting to note that dietary regulation could alter one's genome and genome modifications. Currently, there is a lack of comprehensive study of the alteration of DNA methylation in Indian CAD patients. This study from CSIR-IGIB has analyzed the DNA methylation status of various genes and has highlighted altered methylation in various genes which may discriminate CAD in Indian population.
This work was published in Gene in September 2019. The article is available online at https://doi.org/10.1016/j.gene.2019.144107