[Beta-thalassemia mutations and single nucleotide polymorphism at -158 of Ggamma-globin gene associated with altered levels of Hb F in beta-thalassemia heterozygotes].
OBJECTIVE
To investigate the relationship of beta-thalassemia mutations and the single nucleotide polymorphism(SNP) at position -158 of (G)Gamma-globin gene to the altered levels of fetal hemoglobin(Hb F) of beta-thalassemia heterozygotes.


METHODS
Hb F was quantitated by alkali denaturation; beta-thalassemia mutations were determined by PCR-allelic specific oligonucleotide(PCR-ASO). The SNP at -158 was analyzed by amplification of (G)Gamma gene promoter fragments from the DNA, followed by Xmn I restriction enzyme digestion.


RESULTS
Among 63 cases with beta-thalassemia trait, 15 had Hb F levels above 2% (2.06%-10.44%). Six beta-thalassemia mutations were observed in this study, namely CD41/42(-TTCT), CD17(A-->T), nt28 (A-->G), CD71/72(+A), IVS-II-654(C-->T) and IVS-I-1(G-->T). There was no difference in the incidence of beta-thalassemia heterozygotes of CD41/42, CD17, CD71/72 and IVS-II-654 between 15 cases with Hb F>/=2% and 48 cases with Hb F<2%. Ten (15.9%) heterozygotes of (G)Gamma-158(C-->T)were detected among 63 cases, and 8 of them (53.33%) belonged to the group of Hb F>/=2% while the remaining 2 cases (4.17%) were in the group of Hb F<2%.


CONCLUSIONS
beta-thalassemia mutations of CD41/42, CD17, CD71/72, IVS-II-654 had no influence on Hb F levels, but (G)Gamma-158(C-->T) had a strong association with moderately increased Hb F levels in beta-thalassemia heterozygotes in the Guangxi area of China.
Department of Pediatrics, the Second Affiliated Hospital, he First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, 530007 P.R.China. adjfchen@yahoo.com.cn
Jian-feng
JF
Chen
Gui-fang
GF
Long
Wei-xiong
WX
Lin
Ping
P
Chen
D000328:Adult; D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D017086:beta-Thalassemia / Q000235:genetics*; D055545:gamma-Globins / Q000235:genetics*
D055545:gamma-Globins; D005319:Fetal Hemoglobin