Single gene mutation affects 60 million

An international study has found a genetic mutation that substantially increases the risk of developing heart disease in people from the Indian subcontinent.

The researchers discovered a 25 base pair deletion in the MYBPC3 gene, which encodes the myosin binding protein-C (cMyBP-C), a protein with an important role in maintaining the structure of cardiac muscle and which regulates cardiac contraction.

The mutation was discovered five years ago in two families in India with cardiomyopathy. A wider study of 800 cases of cardiomyopathies and 699 controls confirmed that the mutation was associated with chronic risk of heart failure.

To assess how widespread the mutation was, the team, led by Dr Kumarasamy Thangaraj of the Centre for Cellular and Molecular Biology in Hyderabad, studied samples from 2085 people in 26 countries and found it is restricted to people from India, Pakistan, Sri Lanka, Indonesia and Malaysia.

It was present in people from all Indian-descended ethnic and religious groups in these countries, but was not present in non-Indian populations. About one in 25 of people from these countries carry the mutation, or 60 million people.

The team believes the mutation has bypassed natural selection either because it confers an advantage early in life or, more likely, because it manifests itself after the prime reproductive years.

The haplotypes of carriers show the mutation to have arisen about 33,000 years ago, postdating the first peopling of the subcontinent.

The mutation has been evaluated as having a massive 7.0 odds ratio for carriers. The odds ratio scale ranges from 1.2 for a small effect and 2.0 for a large effect. The ApoE4 mutation for late-onset Alzheimer’s disease has an odds ratio of 3.0.

The researchers hope the discovery will lead to targeted screening and genetic counselling for those at risk.

The study appears online in advance of publication in Nature Genetics.