Variants of organic anion transporter polypeptide 2 gene are not risk factors associated with severe neonatal hyperbilirubinemia

ABSTRACT

Objectives: This study aimed to determine the prevalence of four variants of organic anion transporter polypeptide 2 (OATP2) gene, and their association with severe hyperbilirubinemia. Design: Observational study. Setting: A tertiary university unit. Patients Term infants of Chinese descent. Methods: 175 infants, consisting of 65 admitted for treatment of severe hyperbilirubinemia (with serum bilirubin levels > 250 mmol/L at age 1-2 days or > 300 μmol/L at age ≥ 3 days) and 110 randomly selected inborn infants without severe hyperbilirubinemia during their fi rst month of life, were recruited. Their blood samples were subjected to sequencing analysis of exon 4 and exon 5 of OATP2 gene for detection of c.388A>G, c.521T>C, c.571T>C and c.597C>T variants. Results: The c.388A>G variant was the most common, and the c.521 T>C was least common, being present in 90.9% and 26.9% of the infants, respectively. Forward logistic regression analysis showed that the only signifi cant risk factors associated with severe hyperbilirubinemia among these Chinese infants were exclusive breast feeding (adjusted odds ratio (OR) = 12.5, 95% C.I. 2.9, 53.4; p=0.001), infants with homozygous 211 variant of the UDPG 1A1 gene (adjusted OR = 37.7, 95% C.I. 4.4, 324.1; p=0.001), and G6PD enzyme level <8.5 IU/g Hb (adjusted OR = 7.3, 95% C.I. 3.1, 17.5; p<0.00001). Gestational age, G6PD mutation status, actual G6PD enzyme level, and the 4 variants of the OATP2 gene mutation were not signifi cant risk factors. Conclusion: Variants of OATP2 gene were not signifi cant risk factors associated with severe hyperbilirubinemia in Malaysian Chinese infants.