According to a survey by World Health Organization (WHO), heart diseases take more than 17 million lives approximately a year, which makes them the world's most severe category of diseases. Apart from the well known factors that contribute to developing a heart disease, genetic factors have been taken into consideration too. The first groundbreaking approach at revealing the genes that are linked with the development of heart diseases was taken in collaboration by an international team of scientists that published a study in which the genetic profiles of over 80,000 people were analyzed and taken under study, thus making it the largest heart disease screening study ever so successfully conducted.
By attempting to understand the mechanisms underlying the genetics of human body, new gates can be opened for the further and advanced research. Sure, it will take time and patience but the science of genetics has always provided us with promising results. With the knowledge of the genes linked to heart disease, the specific genes can be specifically targeted, knocked off or in, as per the requirements. Just so many more opportunities hiding behind the genes, underlying beneath our own skins, only waiting to be found!
The study analyzed all the genes and in results, confirmed the existence of the 10 of 12 previously known heart-disease-related genes, and identified 13 new ones. Quite interesting enough, most of the new genes were found to have no relation whatsoever with the previously established factors of the heart diseases like cholesterol levels, high blood pressure, hypertension etc. This implication suggests specifically that there are more therapeutic novelties to be found yet; much more than what we previously thought and what we already know! Fascinating, isn't it?
In this study conducted by Lewis C Becker, Klaus Berger, Joshua C Bis et al. , a meta-analysis of 4 genome-wide association studies of coronary artery disease (CAD) was performed that consisted of 22,233 individual cases with CAD and 64,762 controls from Europe, that was accompanied by genotyping the major association signals in 56,682 additional patients with the CAD. This study was published under the name of 'Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease' and identified 13 new loci associated with CAD that showed risk allele frequencies causing an association per allele, with a 6% to 17% increase in the risk of CAD.
The novel coronary artery disease risk gene loci, mainly, comprises of the following:
1. Chromosome 6q23.2 - TCF21 where the gene TCF21 encodes a transcription factor of the basic helix-loop-helix family which is mesoderm specific. This gene's product is specifically expressed in embryonic epicardium, mesenchyme-derived tissues of lung, gut, gonad, kidney etc.
2. Chromosome 1p32.2- rs17114036 located in PPAP2B (LPP3) gene which encodes the enzyme lipid phosphate phosphohydrolase 3 (LPP3). LPPs are integral membrane proteins that play an important role in catalysing the dephosphorylation reaction of lipid phosphates.
3. Chromosome 7q32.3 - ZC3HC1 where the gene ZC3HC1 codes for a nuclear protein that is known to play an important role in the regulation of cell cycle.
4. Chromosome 9q34.2 - ABO where the gene ABO codes for the proteins related to the first discovered and widely accepted blood group system, ABO.
5. Chromosome 11q23.3 -ZNF259 where the gene ZNF259 plays an important role as a signaling molecule. ZNF259 communicates mitogenic signals from the cytoplasm to the nucleus and interacts with tyrosine kinase receptors.
6. Chromosome 15q25.1 - ADAMTS7 where the gene ADAMTS7 encodes a protein that is a member of the ADAMTS family and takes part in the degradation of cartilage extracellular matrix proteins.
There, of course, are other genes that have been newly discovered, however, only a few of them are mentioned here. The focus should be on how these newly discovered loci affect the metabolic pathways and increase the risks for CAD and other heart related diseases.
However, only three out of the newly found loci expressed significant association with the CAD risk factors; the majority of which weren't found in the previous studies related to CAD. Apart from this, five loci out of the newly discovered CAD risk loci were found to have pleiotropic effects that expressed immense and major association with several other human diseases and traits. It tremendously had a major impact on the study since pleiotropic effects are known to affect the whole genome, in absolutely not just one way. The pleiotropic nature of the genes has also provided the opportunity to evaluate and analyse the linked pathways and the resulting consequences.
The newly revealed gene loci have set the humankind ablaze with an exciting opportunity to dive deep into the mechanisms lying behind the causes the heart diseases and develop novel strategies for the treatment and cure of heart diseases like CAD. How surprising is that there is just so less we know and there is so much more to be found? Interestingly, as the human nature goes, the more you know, the less you explore and the less you (think you) know, the more you explore. With the on-going research work going on, it can be ensured that better and advanced therapeutic developments are soon to arrive. As sir William quotes, "this study, plus our previous studies, means that we are beginning to piece together the pieces of the jigsaw and gain new understanding. We still have a long way to go - but the jigsaw is beginning to come together"
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