Peripheral artery disease is a common disease, which is described as a circulatory problem in which narrowed arteries reduce blood flow to the limbs, which causes pain when walking and can, in serious cases, lead to limb loss. Usually it affects legs, making daily life harder, but it is said that by quitting smoking, exercising and eating a healthy diet people can help themselves. However, now scientists at the RIKEN Center for Integrative Medical Sciences have identified genes associated with this disease.
They teamed up with a number of universities and hospitals in Japan in order to use gene maps in the Japanese population to identify three genes associated with peripheral artery disease. This is the first successful research to identify specific genetic factors with the peripheral artery disease.
This condition is caused by atherosclerosis—deposits of plaque on the inner lining of blood vessels. Atherosclerosis causes other common problems, such as heart attacks and strokes. Peripheral artery disease leads to limb pain and difficulty walking, but it can also cause major cardiovascular and cerebrovascular events. Furthermore, it is estimated to be the third leading cause of death associated with atherosclerosis. Therefore, understanding genetic reasons behind the peripheral artery disease is very important in order to prevent this condition and its consequences.
Research started with collection of genetic information of 735 people who suffered from the peripheral artery disease from the BioBank Japan project. Then researchers compared their genomes with 3,383 people without the condition taken from the general population.
Scientists were looking for simple genetic variations that would be more common in the patients of peripheral artery disease than in the control group of people without the condition. Scientists identified a big number of such genetic variations, called single nucleotide polymorphisms, in patients, but the number was not sufficient to allow researchers to identify which were really significant.
Therefore, next step of the research was to take the 500 most likely candidate gene variations and analyse the genes of a further 1,150 cases and 16,752 controls to look for single nucleotide polymorphisms that were significantly more common in the patients with the peripheral artery disease.
Scientists singled out 13 such genetic variations that were significantly more common in the patients of the condition. To confirm this data they added a further 1,229 cases, which allowed them to identify three gene loci that were clearly associated with the disease. This is enough evidence to say that people with these three gene polymorphisms are particularly vulnerable to the peripheral artery disease.
These three gene polymorphisms were found to be located in the region flanking two different genes. Therefore, scientists needed to figure out which gene out of these two they were affecting and how. The first polymorphism is found on chromosome 13. Scientists discovered that it is associated with the expression of IPO5, which encodes a protein that is involved in cleaning lipoprotein A (part of bad cholesterol) from peripheral arteries.
The second one is associated with a gene, which encodes a receptor of endothelin-1 – a peptide that promotes the constriction of blood vessels and inflammation. The last one was found to be associated with a gene that encodes a histone deacetylase-9 protein, which regulates cell growth and may be responsible for the thick blood vessel walls attributed to the peripheral artery disease.
There are several implications of the results of the study. Kouichi Ozaki, first author of the research, said: “What is important is that although this study does help to identify people who might be at risk for PAD, the findings could also be used to elucidate the mechanism through which PAD arises, and hence could help to identify therapeutic targets for future treatments. It is important to remember, however, that the study was done in a Japanese population, so that there could be different patterns in other populations, and further studies should be done in other groups.”
This research should provide important knowledge needed to fight this rather common disease. But at the end of the article it is important to remind that there are ways to reduce risk of the peripheral artery disease. It is healthy lifestyle and physical exercise, both of which improve life quality significantly.