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A variant TATA box in the bilirubin UDP-glucuronosyltransferase 1 gene promoter does not contribute to neonatal jaundice in the Japanese population
  1. SHOZO WAKU,
  2. YASUHIRO TAKESHIMA,
  3. HAJIME NAKAMURA
  1. Department of Paediatrics
  2. Kobe University School of Medicine
  3. 7-5-1 Kusunoki-cho
  4. Chuo-ku, Kobe
  5. 650-0017 Japan
  6. Department of Public Health
    1. HISAHIDE NISHIO,
    2. KIMIAKI SUMINO
    1. Department of Paediatrics
    2. Kobe University School of Medicine
    3. 7-5-1 Kusunoki-cho
    4. Chuo-ku, Kobe
    5. 650-0017 Japan
    6. Department of Public Health

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      Editor—A variant TATA box (A[TA]7TAA, designated as TA-7) in the promoter region of the bilirubin UDP-glucuronosyltransferase 1 (BUGT1) gene has been reported to accelerate the increase in bilirubin concentration during the first two days of life.1 However, the relation between TA-7 and peak bilirubin concentration in the neonatal period has not been clarified, and it is also unclear as to whether TA-7 influences bilirubin metabolism in infants of different ethnic groups.

      To investigate whether TA-7 is one of the risk factors for neonatal jaundice in the Japanese population, we performed genotyping analysis of the BUGT1 gene in 74 Japanese newborn infants, and measured bilirubin concentrations at 4–5 days of age in healthy infants (n=55) and peak bilirubin concentrations in infants with jaundice requiring treatment, phototherapy, or exchange transfusion (n=19).

      Informed consent was obtained from parents, and infants were enrolled at birth. All infants were born at 37–42 weeks of gestation and weighed more than 2500 g. They showed no blood incompatibility, had a negative direct Coombs test; they had no clinically significant antenatal and intrapartum complications, and no clinically detectable pathology except for jaundice. In healthy infants serum bilirubin concentrations were measured at 4–5 days after birth. In infants with jaundice requiring treatment, peak bilirubin concentrations were used in the analysis.

      The TATA box region of the BUGT1 promoter was amplified with the polymerase chain reaction (PCR) using the primers BUGT1-A (5′-TAACTTGGTGTATCGATTGGTTTTTG-3′1) and BUGT1-B(5’-ACAGCCATGGCGCCTTTGCT-3′1). BUGT1-B was labelled with a fluorescent dye, 6-carboxy-X-rhodamine. An aliquot of each PCR product was electrophoresed on a genetic analyser (ABI PRISM 310; Perkin-Elmer Applied Biosystems, Foster City, CA, USA) and then analysed using the GeneScan analysis software package (Perkin-Elmer Applied Biosystems). The electrophoretogram clearly separated the peaks for a normal TATA box (A[TA]6TAA, designated as TA-6, 90 base pairs of PCR product size) and TA-7 (92 base pairs of PCR product size).

      The results of genotyping analysis of the BUGT1 gene in 55 healthy infants are given in table 1. The one variant homozygote was omitted from the statistical analysis. The serum bilirubin concentration at 4 days of age in this infant was 9.1 mg/dl. In the healthy infants no significant difference was detected in serum bilirubin concentrations at 4 to 5 days of age between normal homozygotes (10.0 (2.7) mg/dl; mean (SD)) and heterozygotes (9.2 (1.5) mg/dl) (p = 0.43, unpaired Student’s t test).

      Table 1

      Clinical data and DNA polymorphism of all infants

      We also analysed 19 infants with jaundice requiring treatment; 18 normal homozygotes and one heterozygote. Thus the TA-7 allele was found in only one of 19 cases. The peak serum bilirubin concentrations in the 18 normal homozygotes were 18.8 (2.29) mg/dl and that in the heterozygote was 15.7 mg/dl. TA-7 allele frequency was calculated to be 0.07, significantly lower than the value of 0.4 found in the North American and Eastern Scottish populations (p < 0.001, χ2analysis with one degree of freedom).2 3 The genotype distribution in the 74 Japanese infants was also significantly different from that found in the North American and Eastern Scottish populations (p < 0.001, χ2 analysis with two degrees of freedom).

      Ethnic differences in the incidence of neonatal jaundice have been reported. Neonatal jaundice occurs more often in East Asian infants than in Caucasian infants.4-6 Even if the presence of TA-7 could affect the metabolism of bilirubin in the neonatal period, it does not explain the high incidence of neonatal jaundice in Japanese infants, because the TA-7 allele frequency is very rare in the Japanese population. In the 74 infants in this study, we detected only one who was homozygous for TA-7, which happened to be a baby who was in the healthy control group. In the 19 infants with jaundice requiring treatment, we found a TA-7 allele in only one heterozygous case.

      In conclusion, our findings indicate that the variant TATA box in the promoter region of the BUGT1 does not contribute to the high incidence of neonatal jaundice in the Japanese population.

      References

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