Sequence-based polymorphisms in members of the apoptosis Bcl-2 gene family and their association with hematocrit level.

Objective: The Bcl-2 family mediates erythropoietin-dependent survival of erythroid progenitor cells and regulates erythropoiesis. We assessed for any association between Bcl-2 family nucleotide variation and hematocrit (HCT) in healthy blood donors.

Methods: We screened Bcl-w, Bcl-x, and Bax (members of Bcl-2 family) using polymerase chain reaction and singlestrand conformation polymorphism analysis. One polymorphism each was found in Bax and Bcl-w. Using these markers, we genotyped the 100 males and 100 females with the highest or lowest HCT in a population of 819 healthy people in Iowa. A comparison of the allelic frequencies and distribution of each polymorphism was made in males versus females, individuals with low versus high HCT, and other subgroups.

Results: One sequence-based polymorphism was found in Bax and Bcl-w having three and two alleles, respectively. No polymorphism was found for Bcl-x. The Bax polymorphism is caused by variation in nucleotide A repeat number (19, 25, 27) at position 360 in 5'-region of Bax. The Bcl-w polymorphism is a G to A transition at 123. The allelic frequencies of Bax polymorphism were significantly different between males and females (P = 0.004). There were no significant associations for Bcl-w polymorphism by gender or HCT level (P > 0.05).

Conclusions: Polymorphism in the 5'-region of Bax was associated with gender-based HCT differences. This is theoretically due to gender-based hormonal effects on gene transcription mediated by the different polymorphisms.