In a paper published today, scientists from deCODE genetics
and colleagues in the US and Europe refine the understanding
of the variant in the TCF7L2 gene that deCODE has linked to
increased risk of type 2 diabetes (T2D). This variant, which
has been widely replicated, appears to confer risk of T2D
by decreasing insulin secretion. Intriguingly, in the same
study, the authors identify another variant of the same gene
that seems to have undergone marked natural selection in East
Asia, roughly concurrent with the advent of agriculture. This
second variant is associated with increased body mass index
(BMI) and altered concentrations of hunger and satiety hormones.
The authors postulate that it may have conferred a significant
advantage
to those faced by the new environmental challenges of settled
agricultural life through its impact on energy
metabolism,
perhaps also in modern times increasing the propensity for
obesity, a major environmental risk factor for T2D. These
findings
underscore the significance of TCF7L2 not only as one of the
best validated risk genes for a common disease
but also
as a point of intersection between human evolution and disease.
The paper, entitled “Refining the impact of TCF7L2
gene
variants on type 2 diabetes and adaptive evolution,” is published
online in Nature genetics, at www.nature.com/ng,
and will
appear in an upcoming print edition of the journal
