Association of biliverdin reductase A gene polymorphisms with neonatal hyperbilirubinemia from Fujian area

Abstract

Objective To assess the association of single nucleotide polymorphisms(SNPs)of biliverdin reductase A (BLVRA) with neonatal hyperbilirubinemia from Fujian area. Methods A total of 286 patients with neonatal hyperbilirubinemia and 250 healthy controls were enrolled.Genotypes of 5 SNPs within BLVRA gene including rs699512, rs1802846, rs7738, rs1637530 and rs2302032 were determined with matrix-assisted laser desorption ionization/time of flight mass spectrometer.The frequencies of genotype, allele, haplotype and their differentiations were analyzed. Results All 5 SNPs had conformed to Hardy-Weinberg equilibrium (all P>0.05). rs699512 and rs1637530 showed a significant difference between the 2 groups in both allelic and genotypic frequencies(all P 0.05). In recessive model, the frequency of rs699512 GG genotype of patients was significantly lower than that of the healthy control group(OR=0.494, 95%CI: 0.276-0.886, P=0.018), while in dominant model, the frequencies of rs699512 GG+ AG and rs1637530 TT+ CT genotype of patients were significantly lower than that of the healthy control group(OR=0.678, 0.627; 95%CI: 0.482-0.954, 0.444-0.885; P=0.026, 0.008). Based on linkage disequilibrium analysis and haplotype construction, rs1637530, rs2302032, rs699512 and rs1802846 locus in the same area.Based on haplotype CGAT, TGGT, CTAT and CGGT had significant differences between the 2 groups(all P<0.05), and could reduce the risk of high blood bilirubin(OR=0.588, 0.687, 0.501; 95%CI: 0.434-0.797, 0.496-0.952, 0.250-1.004). Conclusions rs699512 and rs1637530 may be associated with neonatal hyperbilirubinemia, A allele in rs699512 and C allele in rs1637530 may be associated with significantly increased risk of neonatal hyperbilirubinemia. Key words: Hyperbilirubinemia; Infant, newborn; Biliverdin reductase A gene; Single nucleotide polymorphism