“Genetic mutation leaves South Asians vulnerable to heart disease” reports The Times today, going on to say that up to 60m people of South Asian origin are destined to suffer from heart disease because of a single genetic mutation. The newspaper says that a large genetics study has found that the mutation occurs almost exclusively among people of an Indian background, affecting about 4% of South Asians.
The complex genetic study behind this story looked at the DNA of several hundred people with cardiomyopathy, a potentially fatal disease of the heart. The researchers found those found those with the condition were several times more likely to carry a particular mutant gene. While researchers found an association between having the gene and a greater risk of cardiomyopathy, this study did not explore the exact reasons behind the increased risk. Neither does it explore the reasons for the increased risk in cardiovascular disease – which is different from cardiomyopathy - in these populations.
The identification of a subgroup of people at increased risk of cardiomyopathy may eventually allow doctors to direct care towards them. Importantly though, there are other (sometimes preventable) causes of heart failure that are not the subject of this study. Steps like exercising regularly, following a healthy diet and not smoking are sensible ways to reduce the risks of heart problems.
Where did the story come from?
This study was conducted by Dr Perundurai Dhandapany and colleagues from various academic and medical institutions across India, Pakistan, the United Kingdom and America.
It is unclear whether the study was supported externally, although many of the authors received fellowships and research grants from different organisations. The study was published in the peer-reviewed medical journal Nature Genetics.
What kind of scientific study was this?
This was an extensive study on the association between a particular genetic mutation and increased risk of cardiomyopathy (disease of heart muscle) in people from India.
Cardiomyopathy – the subject of this study - describes several types of diseases of the actual muscle of the heart such as muscle thickening, stiffening, scarring, and stretching/dilation.
This and other factors including high blood pressure, valve disease, heart attack and angina can lead to heart failure. Heart failure occurs when the heart stops working efficiently and cannot pump enough blood around the body to sustain health.
The first part of the study was a case-control study, split into two sections. Researchers first examined 354 individuals with cardiomyopathies (including 33 who had died). These were matched to 238 controls (in terms of ancestry, age, gender and geography).
The researchers were interested in an mutation in a gene called MYBPC3. This gene is used by the body to produce a particular protein but people with the mutation produce an altered version of this protein.
The researchers analysed genetic samples from the cases and controls to see whether the people with the heart disease were more likely to carry the mutated MYBPC3 gene.
To confirm these results the researchers repeated the process with a further 446 cases and 466 matched controls. To determine whether the results were influenced by ancestry the researchers analysed the genetic make up (genotype) of 794 individuals grouped by their ancestry. In particular researchers were concerned with individuals’ genetic proximity to Europeans.
The researchers then went on to examine heart biopsy specimens from two cases. Through this examination they hoped to get a better understanding of how the mutation affects the heart cells. In subsequent studies in heart cells from rats, they explored the effects of the altered protein on the cells. This altered protein is produced differently in individuals who carry the genetic mutation.
A later part of the study involved screening over 6,000 people from 107 ethnic populations (across 35 states in India) for this mutation. To assess whether the mutation also occurred outside India, the researchers analysed 63 world population samples (2,085 individuals).
What were the results of the study?
In the first part of their study, the researchers found that 49 of 354 (14%) Indian people with cardiomyopathy (the case group) carried the mutation, compared with 7 of 238 (3%) controls. This represented a 5.3-fold increase in the likelihood of cardiomyopathy in those carrying the mutation (95% CI 2.26 to 13.06).
In the second group of cases and controls, the association between the mutation and cardiomyopathy was again confirmed. In this portion of the study the mutation increased the odds of the disease by about 7 times (95% CI 3.68 to 13.57).
When screening 6,273 individuals from different regions across India, they found that 287 (4.6%) had the mutation (although their heart disease status was not known).
The mutation was not found in northeast Indians, Siddis (recent migrants from Africa) and Onges (Andaman Islands). The researchers reported that compared to the northern states, the mutation was more common in southern and western states of India. They say that this may in part explain the greater prevalence of heart failure in the south compared to the north and northeast.
In the international sample, the mutation was present in people from Pakistan, Sri Lanka, Indonesia and Malaysia, but was not seen in other population groups from across the world.
What interpretations did the researchers draw from these results?
The researchers conclude that the particular mutation in the gene MYBPC3 is associated with increased risk of heart failure in South Asians.
They say that this particular mutation may be responsible for 4.5% of heart failure cases in these populations. They suggest that screening for this mutation could be used to identify South Asians at risk of heart failure, and could be accompanied by advice to reduce risk through lifestyle changes.
What does the NHS Knowledge Service make of this study?
This large and involved study adds to evidence that a particular mutation in the MYBPC3 gene is linked to increased risk of cardiomyopathy.from south Asia. It combined multiple, recognised research methods to build on the findings of previous studies related to.
Points to note about this study:
- The researchers have been able to confirm this association in different groups of cases and controls, and have noted that the prevalence of the mutation varies across different populations in India. The researchers say that this varying prevalence may account for the differences in prevalence of heart failure between regions of India. However, this is speculation as it was not known whether the people they screened had the heart disease.
- The researchers have explored whether their results may be confounded by 'ethnic strata' in these populations, i.e. they have assessed whether the mutation may have been more common in people with cardiomyopathy because they had a different ethnic background to the controls and not because the mutation causes cardiomyopathy. They conclude that this was not the case.
- They conclude that in the Indian populations they assessed, the mutation accounts for about 4.5% of cases of heart failure. This means that a large number of cases (95.5% of them) have a different ‘cause’. These results should be interpreted in light of the fact that a case control study cannot prove causation, in this case that the gene mutation in question causes cardiomyopathy. It is possible that there are other factors (including environmental ones and genes in other parts of the genome) which could be associated with cardiomyopathies.
- Another important contextual point is that cardiomyopathies are one of several causes of heart failure (along with, for example, high blood pressure, valve disease, heart attack and angina). Additionally, this study was not concerned with cardiovascular disease, which is often labelled as “heart disease” - the term used in the news headlines.
- The study has assessed the increase in risk of cardiomyopathy with this mutation and not of the increase in risk of heart failure itself.
It is not clear how beneficial screening for this mutation would be at this point, as the advice to those carrying it would be the same as to other individuals – to have a healthy diet, exercise, and avoid smoking. Screening might be important in future if treatments were developed that could specifically help those with this mutation.
Sir Muir Gray adds...
You can’t do much about your genes except be aware of them and accept that reducing risks is even more important in this group of people than for others who don't have the gene.