title: The heterozygote advantage of the Chuvash polycythemia VHLR200W mutation may be protection against anemia.
abstract: The germ-line loss-of-function VHL(R200W) mutation is common in Chuvashia, Russia and occurs in other parts of the world. VHL(R200W) homozygotes have elevated hypoxia inducible factor (HIF)-1 and HIF-2 levels, increased hemoglobin concentration, propensity to thrombosis and early mortality. Because the mutation persists from an ancient origin, we hypothesized that there is a heterozygote advantage. Thirty-four VHL(R200W) heterozygotes and 44 controls over 35 years of age from Chuvashia, Russia were studied. Anemia was defined as hemoglobin less than 130 g/L in men and less than 120 g/L in women. Mild anemia was present in 15% of VHL(R200W) heterozygotes and 34% of controls without a mutated VHL allele. By multivariate logistic regression, the odds of anemia were reduced an estimated 5.6-fold in the VHL(R200W) heterozygotes compared to controls (95% confidence interval 1.4-22.7; P=0.017). In conclusion, heterozygosity for VHL(R200W) may provide protection from anemia; such protection could explain the persistence of this mutation.
authors: Chuvash Republic Clinical Hospital No. 1, Cheboksary, Russia.
authors: Galina Y
authors: GY
authors: Miasnikova
authors: Adelina I
authors: AI
authors: Sergueeva
authors: Mehdi
authors: M
authors: Nouraie
authors: Xiaomei
authors: X
authors: Niu
authors: Daniel J
authors: DJ
authors: Okhotin
authors: Lydia A
authors: LA
authors: Polyakova
authors: Tomas
authors: T
authors: Ganz
authors: Josef T
authors: JT
authors: Prchal
authors: Victor R
authors: VR
authors: Gordeuk
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