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On the importance of being heterozygote Effects of Rh-genotype on the physical and mental health of a non-clinical population
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  • Jaroslav Flegr,
  • Lenka Příplatová,
  • Jana Hlaváčová,
  • Blanka Šebánková,
  • Emanuel Žďárský,
  • Šárka Kaňková
Jaroslav Flegr
Univerzita Karlova v Praze Prirodovedecka Fakulta

Corresponding Author:[email protected]

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Lenka Příplatová
Charles University
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Jana Hlaváčová
Charles University
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Blanka Šebánková
Charles University
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Emanuel Žďárský
DPrevence
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Šárka Kaňková
Charles University
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Abstract

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.