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.
Zeng
She Min
SM
Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA, USA.
Yankowitz
Jerome
J
Widness
John A
JA
Strauss
Ronald G
RG
D000483:Alleles; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D005260:Female; D019254:Genes, bcl-2; D006400:Hematocrit / Q000379:methods; D006801:Humans; D007484:Iowa; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D012737:Sex Factors; D013997:Time Factors; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D051017:Apoptosis Regulatory Proteins; C494826:BAX protein, human; C494811:BCL2L1 protein, human; C491073:BCL2L2 protein, human; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein