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Gene mutation may contribute to body weight regulation, obesity
Through mice and human studies, researchers at Boston Children’s Hospital suggest that a rare genetic mutation which can contribute to severe obesity could lead to further questions about weight gain and energy expenditure among obese patients.
“We found other mutations that weren’t as clearly damaging to the gene,” researcher Joseph Majzoub, MD, chief of endocrinology at Boston Children’s Hospital, said in a press release. “It’s possible that some of these more common mutations actually are pathogenic, especially in combination with other genes in the same pathway.”
Joseph Majzoub
According to researchers, the loss of either melanocortin-2 receptor (MC2R) or melanocortin receptor accessory protein (MRAP) in humans can cause severe resistance to adrenocorticotropic hormone, resulting in glucocorticoid deficiency. To study whether changes to melanocortin receptor accessory protein-2 (MRAP2) are associated with human obesity, Majzoub and colleagues conducted coding sequences in obese and control patients from the Genetics of Obesity Study cohort and the Swedish Obese Children’s Cohort.
Four rare heterozygous variants were absent from cohort-specific controls and 1,000 genomes were found in “unrelated, nonsyndromic, severely obese individuals, with all but one variant in the C-terminal region of the protein,” researchers wrote.
Although the rare mutations directly cause obesity in less than 1% of the obese population, other suspected mutations could be more likely to cause obesity, researchers wrote. These findings suggest that MRAP2 disruption could contribute to body weight regulation, prompting a need for further research to confirm these data.
Disclosure: See the study for a full list of disclosures.