Variants of a gene that leads to cells in blood vessels producing too much of a protein heighten the risk of developing varicose veins, according to a study carried out by a group of Indian researchers.

Varicose veins are a widely prevalent condition where veins, typically in the leg, swell and become twisted.

The development of varicose veins is not well understood, remarked Chandrasekharan C. Kartha of the Rajiv Gandhi Centre for Biotechnology (RGCB) in Thiruvananthapuram, a senior author of a paper published recently in PLOS ONE.

Women can get varicose veins during pregnancy and it is often seen in those who need to stand for long periods of time, such as policemen and shop assistants.

There is also a strong genetic component to it. When both parents suffered from the condition, their progeny had 90 per cent risk of developing it too, compared to a 25 per cent to 62 per cent risk when only parent had it and 20 per cent risk when neither parent had been affected, according to a French study cited in the paper.

An analysis of 6,350 hospital patients with varicose veins in Kerala too showed that 85 per cent of them had a family history for the condition, said Sumi Surendran, a scientist at RGCB and the first author of the PLOS ONE paper.

The researchers decided to look at whether a gene know as ‘human forkhead box C2’ (FoxC2) could be involved. This gene is known to be important for blood vessel development, according to Dr. Surendran.

Moreover, variants of this gene have been implicated in another condition where many sufferers went on to develop varicose veins.

For their study, the scientists examined blood and venous tissue samples from those had varicose veins and compared it to similar samples taken from people without the condition.

They found that cells from those with varicose veins showed changes in the FoxC2 gene.

Changes that occurred at four places in the gene were found to be significantly associated with the condition. Furthermore, individuals carrying two or more of those changes in their FoxC2 gene had a seven-fold greater risk than those with just one change in that gene.

Tests showed that FoxC2 protein levels were greatly elevated in cells from varicosed veins. One of the four changes in the gene occurred in the ‘promoter’ region, which regulates when and how much of the corresponding protein is produced. Using venous cells grown in culture, the scientists were able to demonstrate that this gene variant led to increased protein production.

In another experiment, when cultured venous cells were coaxed into producing excess FoxC2 protein, genes associated with arterial development got activated.

Activation of these genes could be disrupting the normal structure of veins, leading to changes characteristic of varicose veins, said Dr. Surendran.

When a person with a high-risk variant of the FoxC2 gene was faced with having to stand for lengthy periods, the vein in their legs might not be able to adapt to the stress, leading instead to changes that produced varicosity, observed Dr. Kartha.

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