title: Multiple Genetic Modifiers of Bilirubin Metabolism Involvement in Significant Neonatal Hyperbilirubinemia in Patients of Chinese Descent.
abstract: The potential for genetic variation to modulate neonatal hyperbilirubinemia risk is increasingly being recognized. A case-control study was designed to assess comprehensive contributions of the multiple genetic modifiers of bilirubin metabolism on significant neonatal hyperbilirubinemia in Chinese descendents. Eleven common mutations and polymorphisms across five bilirubin metabolism genes, namely those encoding UGT1A1, HMOX1, BLVRA, SLCO1B1 and SLCO1B3, were determined using the high resolution melt (HRM) assay or PCR-capillary electrophoresis analysis. A total of 129 hyperbilirubinemic infants and 108 control subjects were evaluated. Breastfeeding and the presence of the minor A allele of rs4148323 (UGTA*6) were correlated with an increased risk of hyperbilirubinemia (OR=2.17, P=0.02 for breastfeeding; OR=9.776, P=0.000 for UGTA*6 homozygote; OR=3.151, P=0.000 for UGTA*6 heterozygote); whereas, increasing gestational age and the presence of -TA7 repeat variant of UGT1A1 decreased the risk (OR=0.721, P=0.003 for gestational age; OR=0.313, P=0.002 for heterozygote TA6/TA7). In addition, the SLCO1B1 and SLCO1B3 polymorphisms also contributed to an increased risk of hyperbilirubinemia. This detailed analysis revealed the impact of multiple genetic modifiers on neonatal hyperbilirubinemia. This may support the use of genetic tests for clinical risk assessment. Furthermore, the established HRM assay can serve as an effective method for large-scale investigation.
authors.affiliation: Laboratory Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, P. R. China; Central Laboratory, Chaozhou Central Hospital Affiliated to Southern Medical University, Chaozhou, Guangdong Province, P. R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Laboratory Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, P. R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Laboratory Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Central Laboratory, Chaozhou Central Hospital Affiliated to Southern Medical University, Chaozhou, Guangdong Province, P. R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Lin
authors.affiliation: Central Laboratory, Chaozhou Central Hospital Affiliated to Southern Medical University, Chaozhou, Guangdong Province, P. R. China.
authors.forename: Xiang-bin
authors.initials: XB
authors.lastname: Zheng
authors.affiliation: Central Laboratory, Chaozhou Central Hospital Affiliated to Southern Medical University, Chaozhou, Guangdong Province, P. R. China.
authors.forename: Fen
authors.initials: F
authors.lastname: Lin
authors.affiliation: Central Laboratory, Chaozhou Central Hospital Affiliated to Southern Medical University, Chaozhou, Guangdong Province, P. R. China.
authors.forename: Li-Ye
authors.initials: LY
authors.lastname: Yang
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001663:Bilirubin / Q000378:metabolism*; D001942:Breast Feeding; D016022:Case-Control Studies; D002681:China; D005260:Female; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005865:Gestational Age; D014453:Glucuronosyltransferase / Q000235:genetics; D006239:Haplotypes; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D051556:Hyperbilirubinemia, Neonatal / Q000235:genetics*; D007231:Infant, Newborn; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D027361:Organic Anion Transporters / Q000235:genetics; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D000099148:UGT1A1 Enzyme
chemical_list: D001663:Bilirubin; D014453:Glucuronosyltransferase; D051547:Heme Oxygenase-1; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D029362:Organic Anion Transporters, Sodium-Independent; D044925:Oxidoreductases Acting on CH-CH Group Donors; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D000099148:UGT1A1 Enzyme; C503999:SLCO1B1 protein, human; C421209:SLCO1B3 protein, human; C496541:HMOX1 protein, human; C019789:biliverdin reductase