The effect of UGT1A1 promoter polymorphism on bilirubin response to hydroxyurea therapy in hemoglobinopathies.
OBJECTIVE
Hydroxyurea is known to reduce ineffective erythropoiesis and thereby hemolysis leading to a reduction in bilirubin levels in patients with hemoglobinopathies. However, the effect of hydroxyurea on hyperbilirubinemia in relation to the UGT1A1 gene promoter polymorphism is not known in Indian patients with different hemoglobinopathies.


METHODS
We studied 112 patients (77 sickle cell anemia, 22 β-thalassemia intermedia and 13 HbE-β-thalassemia) who were on hydroxyurea therapy for 2 years for their response towards hyperbilirubinemia associated with UGT1A1 promoter polymorphism.


RESULTS
The patients with (TA)(7)/(TA)(7) repeats had significantly higher serum bilirubin levels than those with (TA)(6)/(TA)(6) repeats in all the groups and the reduction in serum bilirubin after hydroxyurea therapy was still higher among patients with (TA)(7)/(TA)(7) repeats when compared with (TA)(6)/(TA)(6) repeats.


CONCLUSIONS
Higher bilirubin levels were associated with the (TA)(7)/(TA)(7) sequence however they did not come down to normal levels after hydroxyurea therapy.
Italia
Khushnooma Y
KY
National Institute of Immunohaematology (ICMR), 13th Floor, N M S Bldg, KEM Hospital Campus, Parel, Mumbai 400 012, India. kyitalia4@yahoo.co.in
Jijina
Farah F
FF
Jain
Dipty
D
Merchant
Rashid
R
Nadkarni
Anita H
AH
Mukherjee
Malay
M
Ghosh
Kanjaksha
K
Colah
Roshan B
RB
D000293:Adolescent; D000328:Adult; D001663:Bilirubin / Q000097:blood*; D002648:Child; D017353:Gene Deletion; D014453:Glucuronosyltransferase / Q000235:genetics*; D006453:Hemoglobinopathies / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D055815:Young Adult; D000099148:UGT1A1 Enzyme
D001663:Bilirubin; D014453:Glucuronosyltransferase; D006918:Hydroxyurea; D000099148:UGT1A1 Enzyme