Pharmacogenomics of cardiovascular complications in diabetes and obesity

Abstract

Heart disease is a major cause of death in US and worldwide. The complex interplay of the mechanisms between diabetes, obesity and inflammation raises concerns for therapeutic understanding and developing treatment options for patients. Recent advances utilizing pharmacogenomics has helped researchers to probe in to disease pathophysiology and physicians to detect and, diagnose the disease in patients. The understanding developed in the area primarily addresses the issue focusing on the nature and asks the question 'Why' some individuals respond to the standard medication regimen and others do not. The central idea that genomics play a vital part in how the healthcare providers: physician, pharmacist, and nurse provide treatment utilizing the best practices available for maximum benefits. Pharmacogenomics is the scientific basis which offers the fundamental understanding for diseases, based on which therapeutic approaches can be designed and delivered. The discovery that not all humans respond to the drug in the same way is a 'paradigm shift' in how current therapies are offered. The area of pharmacogenomics at its core is linked to the genetic basis for the disease and the response to treatment. Given that diabetes and obesity are major metabolic ailments globally wherein patients also often suffer from cardiac disorders, a comprehensive genetic and pharmacogenomic understanding of these conditions enable the development of effective therapeutic strategies. In this review, we discuss various pharmacogenomic approaches with special emphasis on heart disease as it relates to diabetes and obesity. Recent information in regard to relevant patents in this topic are also discussed.

Figure 1. Schematic for human cardiac ventricular action potential

The action potential represents the shape and form depicting the involvement of ion channel in manifesting into a complete waveform.

Figure 2. Phenotype of long QT syndrome

The pathway depicts the steps leading to pharmacogenomic phenotype for long QT syndromes. The flow chart shows the starting point with DNA until the cardiovascular phenotype utilized for identification and detection. Important intermediate points such as the RNA, protein and functional changes are shown as discrete steps. The environmental, drug induced influences, epigenetics and congenital categories influence are shown as pharmacogenomics indicators.

Figure 3. Techniques in pharmacogenomics

Use of different techniques in identification of single nucleotide polymorphisms (SNP) and diseases. The classical use of molecular biology concepts for primer design and use along with cDNA hybridization amplification by polymerase chain reaction (A), development of cloning techniques for identification and specific expression of the gene of interest using vector system is shown in (B), the high throughput technique for automating the PCR technique is shown in (C) with gene chip able to hybridize multiple genes in a short period of time. Panel (D) shows the evolution of current day deep sequencer able to provide whole genome information used for mapping of diseases.