(TA)n UDP-glucuronosyltransferase 1A1 promoter polymorphism in Nigerian neonates.
Nigerian neonates have a high incidence of bilirubin encephalopathy. Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is prevalent in this population. (TA)7 promoter polymorphism in the gene encoding the bilirubin conjugating enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1) potentiates hyperbilirubinemia in G-6-PD deficient neonates. We studied (TA)n allele frequency to determine, at least in part, its contribution to the frequency and severity of hyperbilirubinemia. DNA was extracted from umbilical cord blood of sequentially born Nigerian neonates and the (TA)n UGT1A1 promoter sequence determined. The (TA)n allele distribution was compared with reported adults of varying African ancestry and Sephardic Jewish neonates. Among 88 Nigerian neonates, (TA)6 and (TA)7 alleles were almost equally distributed (0.46 and 0.43, respectively). Some individuals with (TA)5 and (TA)8 sequences were encountered. Allele distribution was similar to that of the African ancestry population but differed from the Sephardic Jewish newborns, in whom the (TA)6/(TA)7 distribution was 0.65/0.35. Whereas 45% of Nigerian alleles and 50% of African ancestry alleles, respectively, included a (TA)7 or (TA)8 sequence, only 35% of Jewish alleles were (TA)7 (p < 0.001), and no (TA)8 alleles were encountered. The high frequency of (TA)n promoter polymorphism, coupled with G-6-PD deficiency, may contribute to the pathogenesis of extreme neonatal hyperbilirubinemia in Nigeria.
Kaplan
Michael
M
Department of Neonatology, Shaare Zedek Medical Center, Faculty of Medicine of the Hebrew University, Jerusalem 91031, Israel. kaplan@cc.huji.ac.il
Slusher
Tina
T
Renbaum
Paul
P
Essiet
Dominic F
DF
Pam
Sunday
S
Levy-Lahad
Ephrat
E
Hammerman
Cathy
C
D044383:Black People / Q000235:genetics*; D015331:Cohort Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000235:genetics; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D051556:Hyperbilirubinemia, Neonatal / Q000201:enzymology / Q000235:genetics*; D007231:Infant, Newborn; D007585:Jews / Q000235:genetics*; D009549:Nigeria; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D012720:Severity of Illness Index; D000099148:UGT1A1 Enzyme
D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme