A team of international researchers, led by the University of Exeter, has found a new reason to explain why people who lack a specific blood group are genetically inclined to be overweight or obese. The researchers discovered that those with a genetic variant that disables the SMIM1 gene tend to have higher body weight because they burn less energy when resting. SMIM1 was only discovered a decade ago during the search for the A gene that controls a specific blood group, called Vel, is lacking in one in 5,000 people, making them Vel-negative. New research indicates that this group is more likely to be overweight, potentially leading to the development of new treatments. The researchers are now looking to see if a common thyroid dysfunction drug could be effective in treating obesity in individuals without both copies of the SMIM1 gene.
Additionally, the study discovered that people without both copies of the gene also have other indicators associated with obesity, such as high levels of fat in the blood and signs of fat tissue dysfunction.The study found that there were higher levels of liver enzymes and decreased levels of thyroid hormones. The research was published in Med and received funding from the National Institute for Health and Care Research and the British Heart Foundation. The study involved collaboration with partners from the University of Cambridge, the Sanger Institute, Copenhagen University in Denmark, and Lund University in Sweden. Lead author Mattia Frontini, who is an Associate Professor of Cell Biology at the University of Exeter Medical School, stated that obesity rates have significantly increased in the past 50 years, and it is estimated that by 2030, over one billion people worldwide will be obese.The diseases and complications associated with obesity create a significant economic burden on healthcare systems. Obesity is the result of an imbalance between energy intake and expenditure, which is often influenced by a combination of lifestyle, environmental, and genetic factors. In a small number of cases, obesity can be caused by genetic variants. In these instances, new treatments may be able to help these individuals. Researchers are now considering conducting a clinical trial to determine whether a widely available drug for thyroid supplementation could be effective in treating obesity in individuals who lack the SMIM1 gene. Our findings emphasize the importance of further investigating this issue.The research aims to not only identify the genetic cause of obesity and find the most suitable treatment, but also to decrease the social stigma associated with it.”
In order to make this discovery, the team examined the genetics of almost 500,000 participants in the UK Biobank cohort. They found 104 individuals with the variant that causes loss of function in the SMIM1 gene (46 females and 44 males). The team also collaborated with the NIHR National BioResource to collect fresh blood samples from both Vel negative and positive individuals. This partnership involved NHS Blood and Transplant (NHSBT), which consists of over 100,000 blood donors.s who volunteered for genetic research studies. Based on the data collected from these groups, it is estimated that the SMIM1 variant may play a significant role in obesity for approximately 300,000 individuals worldwide.
The team examined the effects of the SMIM1 gene variant in four additional groups of people. Their findings revealed that the variant had an impact on weight, resulting in an average increase of 4.6kg in females and 2.4kg in males.
Co-author Jill Storry, Adjunct Professor at Lund University, Sweden, commented, “SMIM1 was only discovered recently, but our research suggests that it could have a substantial influence on obesity.”A decade ago, researchers discovered a blood group protein on red blood cells, but its other function has remained a mystery until now. The discovery that it has a more general role in human metabolism is very exciting.”
Co-author Professor Ole Pedersen from the University of Copenhagen in Denmark expressed the team’s anticipation to see how this new knowledge can be used to develop practical solutions for people with this genetic make-up.”
First author Dr. Luca Stefanucci from the University of Cambridge mentioned, “With the increased availability of genetic data and more information on the SMIM1 mechanism, we hope to see that this new knowledge can be applied in real-life scenarios.”When people who don’t have SMIM1 are found, they are given information and assistance.”