Small changes in genes can make us unique, and they can also have biological effects. Scientists have identified a genetic mutation in a gene called SMIM1 that encodes for a blood group called Vel, which is expressed on red blood cells. This mutation leads to a non-functional gene, eliminating that surface protein, and making carriers Vel-negative. Researchers have now determined that this genetic mutation also causes a higher body weight in carriers because these individuals do not use as much energy when they are at rest compared to people with functional copies of SMIM1. The findings have been reported in the journal Med.
Carriers of this rare SMIM1 mutation have a variety of biomarkers of obesity including fat tissue dysfunction, abnormally high levels of liver enzymes and fats in the blood, and lower thyroid hormone levels than normal.
In this work, the researchers analyzed genetic and health data from about half a million people in the UK Biobank. They found 46 females and 44 males with loss-of-function mutations in SMIM1. Therefore, about 300,000 obese people worldwide might be affected by SMIM1 variants or mutations that predispose them to obesity.
In another four cohorts of people, additional SMIM1 variant carriers were found. This data indicated that SMIM1 variants can cause female carriers to carry an extra 4.6 kilograms (10 pounds), and an extra 2.4 kg (5.3lb) in male carriers.
Lead study author and University of Exeter Associate Professor Mattia Frontini noted that rates of obesity have almost tripled within only the past 5 decades, and an estimated one billion people around the world will likely be obese by the year 2030; obesity-related diseases will continue to be a burden on healthcare systems.
"Obesity is due to an imbalance between energy intake and expenditure, often a complex interplay of lifestyle, environmental, and genetic factors," added Frontini. Treatments can sometimes be applied in these situations, but this study has highlighted the importance of identifying genetic causes of obesity, because in some people, obesity is due to genetic variations. These genetic causes should be identified so that better treatments can be found for everyone.
"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. It's very exciting to find that it has a more general role in human metabolism," said study co-author Jill Storry, an Adjunct Professor at Lund University.
Sources: University of Exeter, Med
