When one looks at diseases, it is important to consider that the mutations that cause the disease may confer other selective advantages.
A classic example has been sickle-cell disease. The heterozygous state is usually asymptomatic and makes an individual less prone to malaria. “In the USA, where there is no endemic malaria, the prevalence of sickle-cell anaemia among blacks is lower (about 0.25%) than in West Africa (about 4.0%) and is falling. Without endemic malaria, the sickle cell mutation is purely disadvantageous and will tend to be selected out of the affected population via natural selection.” —Sickle–cell disease – Wikipedia, the free encyclopedia
Another common disorder is hemochromatosis. A recent letter in the New England Journal of Medicine (NEJM 2013; 369: 785-6) explains why having the HFE gene could be advantageous. According to the authors the genetic mutation arose in Celtic populations who were notably taller than other populations. As such, the authors hypothesized that the patients with HFE hemochromatosis would have better growth by having an abundant supply of iron during periods of rapid development.
They assessed a cohort of 176 Swiss patients with HFE hemochromatosis. 93% were homozygous for the C282Y mutation, 7% had a compound H63D-C282Y mutation. All of the patients had verified iron overload determined as a ferritin > 300 mcg/L or a transferrin saturation >45%.
Compared with an age-matched, sex-matched Swiss reference population, men with hemochromatosis (n=120) were 4.3 cm taller on average. In women (n=56), the difference was 3.3 cm. To avoid bias due to population origin, the cohort was also compared with data from Ireland where the data remained validated.
Take-home message: Extra iron in the first two decades of life promote better growth (and probably other advantages). However, iron overload later in life can lead to cirrhosis, diabetes, heart disease, and reproductive problems.
Related blog post:
AASLD Hemochromatosis Guidelines: