Increased resistance to influenza as a possible source of heterozygote advantage in cystic fibrosis.

Cystic fibrosis is the most common lethal or semi-lethal genetic disease in 
Caucasians of Central European origin, among whom it is inherited as 
an autosomal recessive trait at a frequency approximately 10 times that 
expected from recurrent mutation alone. A decreased sialic acid content has 
been observed in cell surface glycoproteins on cystic fibrosis fibroblasts and 
in numerous soluble glycoprotein preparations from cystic fibrosis homozygotes. Sialic acid 
residues on cell surface glycoconjugates play an essential role in the 
binding and infectivity of myxoviruses and paramyxoviruses, including those causing pandemic 
influenza. It is suggested that increased resistance to these viruses conferred 
by similar but quantitatively smaller alterations in sialoglycoconjugate structure in cystic 
fibrosis heterozygotes may have provided a selective advantage to maintain the 
high frequency of the cystic fibrosis gene in Caucasian populations. 