Variation and heritability of Hb F and F‐cells among β‐thalassemia heterozygotes in Hong Kong

AbstractEnhanced fetal hemoglobin (Hb F) production can partially compensate for the lack of adult hemoglobin (Hb A) in patients with β‐thalassemia major or intermedia, and ameliorate the clinical severity of these diseases. To further elucidate factors governing Hb F levels, we evaluated demographic, clinical, laboratory, and genetic characteristics in 241 unrelated adult β‐thalassemia carriers in Hong Kong. They had wide variations in Hb F and F‐cell numbers skewing toward higher levels. Individuals who coinherited the Xmn IT‐allele in the Gγ‐globin gene promoter had higher Hb F and more F‐cells compared with those lacking the Xmn I T‐allele. However, both groups exhibited a similarly wide spread of Hb F and F‐cells. The correlation of Hb F and F‐cells corresponded well to both linear and exponential models, suggesting multiple mechanisms for Hb F augmentation. The heritabilities of Hb F and F‐cells were calculated in 66 families (111 parents who were β‐thalassemia carriers and 82 asymptomatic offspring) to be 0.7 to 0.9. The Xmn I polymorphism accounted for 9% of the Hb F and 13% of the F‐cell heritabilities. These results suggest that these family members are well suited for genome wide association studies that will identify genetic loci regulating Hb F production, and likely novel pharmacological targets for reactivating Hb F production in adults. Am. J. Hematol., 2008. © 2008 Wiley‐Liss, Inc.

Variation and heritability of Hb F and F‐cells among β‐thalassemia heterozygotes in Hong Kong Journal Articles