Could a missing gene make it harder to lose weight?

Many people find it difficult to maintain a healthy weight. But what if your genes are the reason you struggle to lose weight? 

That’s what UK media outlets suggested after a study found people with a rare fault in their genes are at increased risk of obesity. 

The research of 488,376 people enrolled in the UK Biobank programme looked at the differences in health between those with and without a gene known as SMIM1.  

It found the few people missing the gene were 27 per cent more likely to have a body mass index classed as obese (BMI greater than 30) than those who had it. 

Women missing the gene weighed an extra 4.6kg (10 lbs) on average, while men were 2.4kg (5.3 lbs) heavier than those who had the gene, reported the BHF part-funded study in the journal Med. 

They also had higher levels of a type of fat (called triglycerides) in their blood, even after the results were adjusted for having obesity (a high BMI), and were more likely to have signs of liver damage. 

The reason for their excess weight was likely because they burned fewer calories when resting compared to those with the SMIM1 gene, reported the University of Exeter researchers after carrying out more research on 12 people without the gene. 

This could be because they had a mildly underactive thyroid (hypothyroidism), which slows the rate at which the body converts food and drink to energy, they added after finding these 12 people had lower than average levels of thyroid hormones in their blood. 

The SMIM1 gene was discovered about 10 years ago.  

Two copies of the gene are needed for it to work properly. 

However, around one in 5,000 people in the UK have no copies of the gene, making it a rare genetic condition, according to this latest study.  

All those missing the gene were White and of European ancestry, leading the researchers to estimate that 200,000 people worldwide could be affected. 

What do the researchers say?

On the back of the findings, the researchers suggested that people already living with excess weight or obesity could be prescribed levothyroxine, a medicine used to treat people who have an underactive thyroid. 

“In a small minority of people, obesity is caused by genetic variants”, said the study’s lead author Professor Mattia Frontini in a press release from the University of Exeter. 

“When this is the case, new treatments can sometimes be found to benefit these people – and we’re now hoping to run a clinical trial to find out whether [a] widely-available drug for thyroid supplementation may be beneficial in treating obesity in people who lack SMIM1,” added Professor Frontini, an associate professor of cell biology. 

The researchers also said that genetic testing could help those missing the SMIM1 gene to take steps to manage their weight and reduce the risk of excess weight earlier in life. 

How good was the research? 

The researchers realised that, because the missing gene is so rare, the sample size for their initial UK Biobank-based study was too small. 

So, they carried out four further studies to verify the findings. 

One UK study measured how many calories 12 people without SMIM1 burned at rest compared to 310 people with the gene.  

They were recruited from 1.4 million people taking part in the National Institute for Health and Care Research National BioResource. 

They also looked at 90,000 participants in the Danish Blood Donor Study.  

From which they identified 43 people without SMIM1 and compared them to 645 people of the same age and sex who did have the gene. 

They found women without SMIM1 weighed more on average, but there was less of an obvious difference in weight in men missing the gene compared to those who had it. 

They also confirmed 30 had the missing gene out of 90,700 people in the Copenhagen Hospital biobank and compared them to 450 people with SMIM1 of the same age and sex. 

Both Danish studies found that those without SMIM1 were more likely to use statins, which are prescribed to help lower high cholesterol. 

Finally, they compared data from 60 people missing the gene recruited from the US Million Veteran Program and found they were more likely to be living with excess weight or obesity compared to 428,082 with the gene. 

However, because the research involved using data and participants from several clinical studies, it was hard to accurately compare the results, the researchers admitted. 

Other factors such as diet and exercise, which the researchers did not know about, may also have affected participants’ weight and health, they said. 

How good was the media coverage?

The study was covered by the Daily Mail and The Times.

The Daily Mail wrote that levothyroxine “may be a cure” for people without both copies of the SMIM1 gene. 

This is potentially misleading as further research is needed to confirm if this medicine could help people missing the gene lose weight. 

And while both outlets explained that the genetic fault increased the risk of obesity, they did not mention that the researchers could not rule out other factors that could have affected participants’ risk of having excess weight, such as their lifestyle.

There was also some confusion about how many people around the world may be missing the gene, as a University of Exeter press release incorrectly reported that figure was 300,000, not 200,000 as stated in the study. 

BHF Verdict

We know that excess weight and obesity can be caused by many different things, including your genes. 

But while this new study suggests that lacking the SMIM1 gene may increase your risk of obesity, it also found that this specific genetic variation is very rare. 

In the UK, over one in four people live with obesity and nearly two in five have excess weight, compared to just one in 5,000 with the faulty gene. Also, further research is needed to see if the medication levothyroxine could help those affected. 

So, whether you have the gene or not, there are plenty of lifestyle changes you can make to help lower your weight and reduce the risk of heart and circulatory diseases. 

This includes eating a Mediterranean diet with lots of vegetables, fruits, oily fish and beans, and staying active with regular exercise. 

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