Extreme thinness could be genetic
While there’s a lot of talk about obesity, millions of people also suffer from extreme or pathological thinness, which can even be a contributing factor to life threatening diseases.
While worrying in adults, the repercussions of extreme thinness can be doubly difficult, with parents being blamed for under-feeding their children. Researchers have just identified, for the first time, a genetic anomaly behind extreme thinness, which could well be the beginnings of finding a treatment.
The chromosome linked to obesity and extreme thinness
A year after evidence of the role played by a region in chromosome 16 in obesity was established, researchers at the genomics and metabolic disorders laboratory (CNRS/Lille 2 University/Pasteur Institute of Lille) and at Imperial College (London) led by Prof Philippe Froguel, in collaboration with Jacques S. Beckmann’s team in Lausanne, have discovered that this same region is also linked to extreme thinness, which is characterised by a body mass index of less than 18.5 (BMI = the relation between weight in kg to size in metres squared) and a risk of death multiplied by 3.
23 times more risk of extreme thinness
According to the study, carried out on 100,000 people, individuals who carried the three copies of this chromosomal region had 23 times more risk of extreme thinness if they were men, and 5 times more risk if they were women. As many as one person in 2,000 could carry this genetic anomaly.
Among those children affected by extreme thinness, half also demonstrated learning difficulties, while a quarter of the group of study participants suffered from microcephaly, a disease in which the head and brain are abnormally small, and which is also associated with neurological problems and shorter life expectancy.
In 2010, the same Anglo-French and Swiss teams had discovered that in cases where there was one copy of this fragment of chromosome 16 – known to be subject to fluctuations in copies of its genes – the risk of severe obesity was multiplied 43 times, which explained 1% of cases (this study is available in English).
By pursuing their work in this chromosomal region, evidence that this anomaly has an inverse effect has now been established, and we now know that an excess of genes in this area can cause the opposite effect, extreme thinness. In two thirds of cases, this genetic anomaly known as ‘trisomy’ (three copies instead of two) is hereditary; that’s to say that it is already present in the mother or father. For Philippe Froguel, this discovery is, “the first example of the duplication or lack of a part of the genome causing opposite effects”.
Finding the thinness gene
However, researchers remain ignorant of the mechanisms behind these physical characteristics. The next step in their studies will be to identify which of the 28 genes present in this region of chromosome 16, linked to the phenomena of obesity and extreme thinness, are responsible for appetite and weight.
"One reason this is important is that it shows that failure to thrive in childhood can be genetically driven. If a child is not eating, it's not necessarily the parents' fault" says Prof Froguel. “If we can work out why gene duplication in this region causes thinness, it might throw up new potential treatments for obesity and appetite disorders.”
- “Gene overdose’ causes increases risk of extreme thinness,” Press release, Imperial College, September 2011
- “Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus,” S. Jacquemont, P. Froguel et al., Nature 478, 97-102, October 2011
Copyright © 2011 Doctissimo
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