Analysis Of SLCO1B1 And UGT1A1 Gene Polymorphisms In Neonatal Hyperbilirubinemia

Objective To study the characteristics of solute carrier organic anion transporter family member 1B1 (SLCOIB1) gene c.388A>G, c.521T>C, c.571T>C, c.597 C>T polymorphisms and uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) gene c.211G>A polymorphism in neonatal hyperbilirubinemia of our region, and to evaluate the association of SLCO1B1 and UGTIAI gene polymorphisms with the occurrence of neonatal hyperbilirubinemia.Methods 1.SLCO1B c.388A>G, c.521T>C and UGT1A1 c.211 G>A genotypes in all subjects (case group:203 cases; control group:169 cases) were identified by the polymerase chain reaction --restriction fragment length polymorphism (PCR-RFLP) method and SLCO1B c.571T>C and c.597 C>T genotypes in a part of subjects (case group:121cases; control group:87cases) were tested by gene sequencing method.2.The allele frequencies of SLCOIBI and UGT1A1 gene variations were compared between case group and control group, and the association of SLCO1B1 and UGT1A1 gene polymorphisms with the risk of neonatal hyperbilirubinemia was evaluated.Results 1. Five types of gene polymorphisms (SLCO1B1 gene c.388A> G, c.521T>C, c.571T>C, c.597 C>T and UGT1A1 gene c.211G>A)were detected in this study. Their variant rate in the subjects were 93.0%,23.9%, 39.9%,85.6% and 34.7%, respectively.2. The allele frequencies of SLCO1B1 gene c.388A>G, c.521T>C, c.571T>C and c.597 C>T polymorphisms in patients and the controls was (0.776 vs 0.793), (0.116 vs 0.133), (0.244 vs 0.213), (0.612 vs 0.569) (P>0.05).3. The odd ratio (OR) and 95% confidence interval (CI) of the relationship between the occurrence of neonatal hyperbilirubinemia and SLCO1B1 gene c.388A>G, c.521T>C, c.571T>C and c.597 C>T variations were 1.085(0.371,3.168),1.156(0.618,2.160),0.868(0.494,1.526)and 0.930 (0.426,2.032) (P>0.05), respectively.4. The allele frequencies of UGT1A1 gene c.211G> A mutation in patients and the controls was 0.251 vs 0.109. There were significant differences when it was compared between the two groups (P<0.05). Compared with control group, the A allele frequency of the case group was significantly higher (P<0.05). The OR and 95% CI of the relationship between the occurrence of neonatal hyperbilirubinemia and UGT1A1 gene c.211G>A polymorphism were 2.957 (1.871,4.672) (P<0.05).5. The OR and 95%CI of the relationship between the occurrence of neonatal hyperbilirubinemia and those who carried UGT1A1 gene c.211G> A variation combined with SLCO1B1 gene c.388A>G variation were 1.944 (0.670,5.639) (P>0.05).Conclusions 1.There are SLCO1B1 c.388A> G, c.521T> C, c.571T> C and c.597 C> T polymorphisms in our study population.2. Each single polymorphism of SLCO1B1 gene c.388A>Q c.521T> C, c.571T>C and c.597 C>T may not be associated with neonatal hyperbilirubinemia in our research population.3. Neonates who carry the c.211G> A polymorphism in UGT1A1 gene are at high risk to develop neonatal hyperbilirubinemia in our region.