The heterozygote advantage of the chuvash polycythemia VHL R200W mutation may be protection against anemia
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. © 2011 Ferrata Storti Foundation.
Miasnikova, Galina Y.; Sergueeva, Adelina I.; Nouraie, Mehdi; Niu, Xiaomei; Okhotin, Daniel J.; Polyakova, Lydia A.; Ganz, Tomas; Prchal, Josef T.; and Gordeuk, Victor R., "The heterozygote advantage of the chuvash polycythemia VHL R200W mutation may be protection against anemia" (2011). The Center For Sickle Cell Disease Faculty Publications. 101.