A new genetic variant linked with obesity has been discovered, which could help explain weight gain for hundreds of thousands of people worldwide.
The researchers believe their findings may unlock new obesity treatments and are hoping to run a trial to see if a widely available, low-cost thyroid medication might be of value.
The genetic variant is a 17-nucleotide deletion that affects the small integral membrane protein (SMIM)1 and underlies a particular blood group known as Vel.
The research, published in the journal Med, showed that people without a working SMIM1 gene expended less energy while resting, resulting in average extra weight of between 2 and 5 kg.
“SMIM1 was only discovered a decade ago, as a long-sought blood group protein on red blood cells, but its other function has remained unknown until now,” explained researcher Jill Storry, PhD, from Lund University.
“It’s very exciting to find that it has a more general role in human metabolism.”
Fellow investigator Ole Pedersen, PhD, from the University of Copenhagen, added: “The whole team is very much looking forward to seeing how this new knowledge can be translated into practical solutions for people with this genetic make-up.”
Obesity rates have nearly tripled worldwide in the past 50 years and by 2030 it is estimated that a billion people will have obesity. While this is due to an imbalance between energy intake and expenditure, it is caused by genetic variants in a small minority of people.
The researchers studied the genetics of nearly half a million UK Biobank participants to determine whether loss of function in SMIM1, consisting of a homozygous genotype, was associated with additional traits other than the known blood ones.
This identified 46 women and 44 men with the SMIM1−/− genotype, known as the Vel-negative blood group, 90 of whom were unrelated and of European ancestry.
The investigators also compared fresh blood samples from people with different genotypes and confirmed their findings using four other cohorts.
The research suggested at least 200,000 people have the variant worldwide and it is present in one in 5000 British people, with a higher frequency in Scandinavian countries.
The SMIM1−/− genotype was associated with women carrying an extra 4.6 kg and men carrying an extra 2.4 kg.
These people also showed a combination of metabolic features including excess fat mass, inflammation, altered liver function, triglycerides, and altered lipoprotein metabolism that were due, at least in part, to reduced energy expenditure.
There were also signs of hypothyroidism with normal thyroid-stimulating hormone but low levels of free thyroid hormone.
“The rapidly growing amount of genomic data available, including blood donors typed by arrays, means that more and more SMIM1−/− individuals will be identified as part of the incidental findings,” the authors noted.
“Those who received a test early in life should be advised to monitor their energy intake, while individuals already overweight or [obesity], could be treated with a levothyroxine supplementation, an extremely cost-effective option compared with the most recent recommendations for the treatment of obesity.”
