On the importance of being heterozygote Effects of Rh-genotype on the
physical and mental health of a non-clinical population
Human populations, especially European, are polymorphic in the RHD gene.
A significant fraction of their members carries two copies of a mutated
(deleted) allele, which results in their Rh-negative blood type.
Theoretically, this polymorphism should be unstable. Carriers of the
less frequent allele are penalized by reduced fertility because of the
immunization of Rh-negative mothers by their Rh-positive babies, which
results in hemolytic disease of newborns in their subsequent progeny.
For about 90 years, some form of balancing selection has been suspected
to sustain this polymorphism. Several recent studies showed that the
Rh-positive heterozygotes express higher viability than both types of
homozygotes. However, the genotype of subjects in these studies was
estimated only by indirect methods. Here we compared the physical and
mental health of 178 women and 86 men who were directly tested for their
Rh genotype. The results showed that Rh-positive homozygotic women had
worse and Rh-positive homozygotic men better physical health than
Rh-negative homozygotes; the difference between Rh-negative homozygotes
and heterozygotes was not significant. Our results confirmed that health
of Rh-positive heterozygotes and homozygotes differ. Therefore, any
result of the comparison of subjects with Rh-positive and Rh-negative
phenotype depends on the heterozygote-to-homozygote ratio in the
Rh-positive sample. It is, therefore, crucial to analyze the effects of
Rh-genotypes, not phenotypes in future studies.