Proconvertase Gene Linked to Obesity

As unequivocally documented by twin studies, obesity is one of the most heritable complex traits. However, so far only a handful of genes that may play a role in the common “garden variety” of obesity (i.e. not just the rare monogenic forms) have been identified .

This week, a large research team led by Philippe Froguel (Picture) that included scientists from France, Denmark, Sweden, Germany and the UK report in Nature Genetics that relatively common variants of the PCSK1 gene, which codes for the proconvertase enzyme are associated with higher BMI. This enzyme is responsible for producing fully functioning versions of hormones such as insulin and glugagon that play important roles in carbohydrate metabolism but also for melanocortin, a key regulator of satiety.

Although the identified variants of the PCSK1 gene cause only relative minor functional changes in this enzyme, the effect on the relevant hormones is quite significant.

Obviously, no single gene or variant thereof can account for all of obesity and there is no reason to believe that all obesity is the same. Rather, it is clear that the heritability of obesity must be due to the distribution of a large number of variants of numerous genes in the population.

So when do we begin using genetic testing in our obesity clinics – not for a while I am guessing, i.e. till we can actually show that specific genes also predict better (or worse) outcomes with specific treatments.

In the dark, all cats are grey.

Edmonton, Alberta