Glucose-6-phosphate dehydrogenase deficiency, the UDP-glucuronosyl transferase 1A1 gene, and neonatal hyperbilirubinemia

Huang, Ching‐Shan; Chang, Pi-Feng; Huang, May-Jen; Chen, En-Sung; Chen, Wu-Charng

doi:10.1053/gast.2002.34173

Cited by 76 publications

(72 citation statements)

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“…We also showed that the occurrence of the A(TA) 7 TAA allele was relatively rare (14.3 versus 40%) and that the variation rate within the coding region of the UGT1A1 gene was much higher (29.3 versus 0.1%) in Taiwanese compared with whites (22). Our previous research indicated that the variation at nucleotide 211 of the UGT1A1 gene was highly related to neonatal hyperbilirubinemia (12,16). As severe hyperbilirubinemia still occurs in Taiwanese neonates, it is necessary to understand the real cause(s) of this disease.…”

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confidence: 66%

“…Recently, another genetic defect, a variation in the promoter area or within the coding region of the UGT1A1 gene, was associated with neonatal hyperbilirubinemia in whites and in Japanese and Taiwanese, respectively (8 -12). It has been determined that the A(TA) 7 TAA promoter variant or homozygous G to A variation at nucleotide 211 in the UGT1A1 gene is an additive risk factor for neonatal hyperbilirubinemia in G6PD-deficient white (13)(14)(15) and Taiwanese neonates (16).…”

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Risk Factors for Severe Hyperbilirubinemia in Neonates

et al. 2004

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The incidence of severe neonatal hyperbilirubinemia is higher in Asians than in whites. A case-control study was designed to investigate the effects of eight known risk factors [breast feeding, ABO incompatibility, premature birth, infection, cephalohematoma, asphyxia, glucose-6-phosphate dehydrogenase (G6PD) deficiency, and variant UDP-glucuronosyltransferase 1A1 (UGT1A1) gene] and a suspicious analog [organic anion transporter 2 (OATP 2) gene] on severe hyperbilirubinemia in Taiwanese neonates. The 72 study subjects and 100 hospital control subjects consisted of neonates with peak serum bilirubin levels Ն342 M and Ͻ256.5 M, respectively. The PCR-restriction fragment length polymorphism method was applied to detect the UGT1A1, OATP 2, and G6PD genes. Bilirubin is mainly produced in its unconjugated form by the turnover of erythrocytes. It may be transported by the organic anion transporter 2 (OATP 2) (1), and it is then conjugated with glucuronic acid through reaction with UDP-glucuronosyltransferase 1A1 (UGT1A1) in the liver before being excreted into the bile (2). The bilirubin level in neonates is much higher than in adults because the life span of the erythrocytes is relatively short and the capacity for bilirubin elimination is lower than in adults (3). The peak serum levels of unconjugated bilirubin in full-term Asian and American-Indian neonates are double those in white and black populations (4). The incidence of severe hyperbilirubinemia and kernicterus is also higher among newborn Asian infants (3). These findings suggest that genetic factors may be involved in the development of severe neonatal hyperbilirubinemia.Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common genetic defect, affecting Ͼ400 million individuals worldwide (5). Furthermore, G6PD deficiency was the main risk factor for development of severe hyperbilirubinemia in Taiwanese neonates in the past (6). The situation has improved, however, since neonatal G6PD screening tests and health education were instituted at the Cathay General Hospital (CGH) in Taipei and nationwide in Taiwan in 1981 (7) and 1987 (6), respectively. Recently, another genetic defect, a variation in the promoter area or within the coding region of the UGT1A1 gene, was associated with neonatal hyperbilirubinemia in whites and in Japanese and Taiwanese, respectively (8 -12). It has been determined that the A(TA) 7 TAA promoter variant or homozygous G to A variation at nucleotide 211 in

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Risk Factors for Severe Hyperbilirubinemia in Neonates

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“…They also observed that neither G6PD deficiency nor UGT1A1 mutations alone increase the occurrence of hyperbilirubinemia. Huang et al 16 found a similar increased risk of hyperbilirubinemia in G6PD deficient Taiwanese infants homozygous for a UGT1A1 variant. The most frequent UGT1A1 promoter variant is reported to affect up to 36% of Africans.…”

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Glucose-6-phosphate dehydrogenase deficiency in triplets of African-American descent

Turbendian

Perlman

2006

J Perinatol

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Despite the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in African Americans, the disorder maybe often overlooked as a diagnosis in the absence of overt signs of hemolysis in neonates with hyperbilirubinemia. We present a case report of anemia and prolonged hyperbilirubinemia due to G6PD deficiency in the absence of hemolysis in dichorionic, triamniotic, preterm triplets of African-American descent.

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“…Arrows highlight variants previously shown to be associated with human-health phenotypes in either multiple human subject studies or in individual association studies involving more than 100 human subjects; these include the UGT1A8*2 allele, 70,71 the three non-synonymous coding SNPs in UGT1A7 (*2,*3,*10), 69,72,73,81,82 two nsSNPs in UGT1A6 (*2,*3), 67,68,70 rs887829 -the SNP revealing the strongest association with tranilast-induced hyperbilirubinemia, 28 and the UGT1A1*6 allele. 10,24,25,[50][51][52][53][54][55][56][57][83][84][85][86][87] Figure 4 Two-point LD maps for variants of UGT1A1, UGT1A6, and UGT1A9 mapped by population. The patterns of pairwise LD, summarized by |D 0 |, include 60 variants in African-Americans (left), 52 in European-Americans (center), and 49 in Asians (right).…”

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confidence: 99%

Comparative genomics analysis of human sequence variation in the UGT1A gene cluster

et al. 2005

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Common polymorphisms within the human UGT1A gene locus are associated with irinotecan and tranilast toxicity. To uncover additional functional variation across this gene cluster, cross-species sequence comparisons were performed. Evolutionarily conserved segments (a total of 47.1 kb) were re-sequenced in 24 African-American, 24 European-American, and 24 Asian individuals, and 381 segregating sites (including 123 singletons) were identified. Highly conserved coding sites were less likely to be polymorphic than diverged sites (Po0.0001) but this pattern was not observed at noncoding sites (P ¼ 0.1025). Among coding variants, the distribution of those computationally predicted to affect function was skewed toward low frequencies. Some alleles occurred at similar frequencies in each population; others had wide disparities. Although strong linkage disequilibrium was detected among the hepatically expressed genes, the degree of linkage disequilibrium varied among populations. These results suggest that rare functional gene variants and inter-population variability must be considered in the interpretation of association studies between UGT1A and drug metabolism/toxicity phenotypes.

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Glucose-6-phosphate dehydrogenase deficiency, the UDP-glucuronosyl transferase 1A1 gene, and neonatal hyperbilirubinemia

Cited by 76 publications

References 19 publications

Risk Factors for Severe Hyperbilirubinemia in Neonates

Risk Factors for Severe Hyperbilirubinemia in Neonates

Glucose-6-phosphate dehydrogenase deficiency in triplets of African-American descent

Comparative genomics analysis of human sequence variation in the UGT1A gene cluster

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