Mutation in MC4R Gene Increases Risk of Obesity, Study Suggests

Mutation in MC4R Gene Increases Risk of Obesity, Study Suggests
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A specific mutation in the melanocortin-4 receptor (MC4R) gene is associated with higher risk of obesity, according to a study.

The study, “Association between MC4R rs17782313 genotype and obesity: a meta-analysis,” was published in the journal Gene.

While it is well known that diet and physical inactivity are major factors in the development and progression of obesity, some people become obese despite living healthy lifestyles. In these cases, genetics likely plays a major role.

Mutations in the MC4R gene and its associated cellular pathway have been linked to obesity. This pathway is involved in appetite regulation, controlling the sensations of hunger and satiety (feeling full). It is currently the target of a potential treatment called setmelanotide.

A change in a single nucleotide — these are the building blocks of DNA — in the MC4R gene, known as rs17782313, has been associated with obesity. Yet studies conducted so far have had limitations, such as not differentiating overweight from obese, or not including a diverse group of people.

Researchers from the Chongqing General Hospital in China conducted a meta-analysis to better assess the relationship between the gene variant and obesity. Meta-analyses are statistical assessments combining the results of several studies on a given topic.

The team searched literature across four online databases. Six studies were deemed eligible, involving a total of 3,133 obese and 3,123 normal-weight participants.

Researchers used five different statistical models to help evaluate whether a particular allele (gene copy) contributes to a higher risk of disease. Each person inherits two alleles of a given gene — one from the mother and one from the father.

They found that allele B of MC4R — rs17782313 — was significantly associated with obesity across four statistical models.

A person with an allele carrying the rs17782313 variant is 1.32 to 1.92 times more likely to be obese than a person with the normal gene copy version (allele A).

People with this genetic alteration in both MC4R gene copies showed an even greater likelihood of becoming obese, as they were 2.3 times more susceptible to obesity than those with unchanged MC4R, according to data from the three studies identified as high quality.

The link between having rs17782313 in only one gene copy and obesity needs to be further clarified, the scientists said.

“Mutated MC4R rs17782313 is associated with higher risk of obesity,” they said. “More high-quality studies and mechanism research are required to help people with mutant allele[s] to manage their body weight wisely.”

Iqra holds a MSc in Cellular and Molecular Medicine from the University of Ottawa in Ottawa, Canada. She also holds a BSc in Life Sciences from Queen’s University in Kingston, Canada. Currently, she is completing a PhD in Laboratory Medicine and Pathobiology from the University of Toronto in Toronto, Canada. Her research has ranged from across various disease areas including Alzheimer’s disease, myelodysplastic syndrome, bleeding disorders and rare pediatric brain tumors.
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José holds a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.

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Iqra holds a MSc in Cellular and Molecular Medicine from the University of Ottawa in Ottawa, Canada. She also holds a BSc in Life Sciences from Queen’s University in Kingston, Canada. Currently, she is completing a PhD in Laboratory Medicine and Pathobiology from the University of Toronto in Toronto, Canada. Her research has ranged from across various disease areas including Alzheimer’s disease, myelodysplastic syndrome, bleeding disorders and rare pediatric brain tumors.
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