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The heterozygote advantage of the Chuvash polycythemia VHLR200W mutation may be protection against anemia

By Galina Y. Miasnikova, Adelina I. Sergueeva, Mehdi Nouraie, Xiaomei Niu, Daniel J. Okhotin, Lydia A. Polyakova, Tomas Ganz, Josef T. Prchal and Victor R. Gordeuk


The germ-line loss-of-function VHLR200W mutation is common in Chuvashia, Russia and occurs in other parts of the world. VHLR200W 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 VHLR200W 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 VHLR200W 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 VHLR200W heterozygotes compared to controls (95% confidence interval 1.4–22.7; P=0.017). In conclusion, heterozygosity for VHLR200W may provide protection from anemia; such protection could explain the persistence of this mutation

Topics: Brief Reports
Publisher: Ferrata Storti Foundation
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Provided by: PubMed Central
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