UGT1A1 gene polymorphisms in North Indian neonates presenting with unconjugated hyperbilirubinemia.
Genetic factors are implicated in pathogenesis of neonatal hyperbilirubinemia. In this nested case-control study, we determined 1) frequency of thymine-adenine (TA)n promoter polymorphism and Gly71Arg mutation in uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene in neonates > or =35-wk gestation presenting with bilirubin levels > or =18 mg/dL and controls, 2) interaction among (TA)n promoter polymorphism, glucose-6-phosphate dehydrogenase (G6PD) gene mutations, and peak bilirubin. The number of TA repeats was assessed by PCR-single-strand conformation polymorphism (SSCP) analysis and Gly71Arg mutation by PCR-RFLP. Fifty samples of both mutations were verified with DNA sequencing. One hundred twenty-seven neonates were enrolled (77 hyperbilirubinemics, 50 controls). The incidence of (TA)n polymorphism was higher in babies with hyperbilirubinemia [89.6% vs. 50%, OR 8.63 (95% CI, 3.2-24.1)]. Gly71Arg mutation was not found either in hyperbilirubinemics or controls. A novel polymorphism (Ala72Pro) at codon position 72 of exon 1 was detected in all 50 samples (21 hyperbilirubinemics, 29 controls), which were sequenced. Presence of variant (TA)n promoter (adjusted OR, 10.6; 95% CI, 3.3-34.2), G6PD deficiency (adjusted OR, 20.6; 95% CI, 3.6-117.3), and history of jaundice in sibling requiring phototherapy (adjusted OR, 12.6; 95% CI, 1.1-141.6) were independent risk factors for bilirubin levels > or =18 mg/dL.
Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Sunil K
SK
Agrawal
Praveen
P
Kumar
Ritu
R
Rathi
Neeraj
N
Sharma
Reena
R
DAS
Rajendra
R
Prasad
Anil
A
Narang
D001483:Base Sequence; D001663:Bilirubin / Q000097:blood; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005865:Gestational Age; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051556:Hyperbilirubinemia, Neonatal / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D007194:India / Q000453:epidemiology; D007231:Infant, Newborn; D007565:Jaundice / Q000503:physiopathology; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012091:Repetitive Sequences, Nucleic Acid; D000099148:UGT1A1 Enzyme
D001663:Bilirubin; D005954:Glucosephosphate Dehydrogenase; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme