Co-Inheritance of G6PD Deficiency and 211 G to A Variation of UGT1A1 in Neonates with Hyperbilirubinemia In Eastern Guangdong

Abstract

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency, which may manifest as neonatal hyperbilirubinemia, is the most prevalent erythrocytic enzyme-related disease in the world.Objective: To investigate the association between neonatal hyperbilirubinemia and co-inheritance of G6PD deficiency and 211 G to A variation of UGT1A1 in Chaozhou city of eastern Guangdong province, the effects of G6PD deficiency and UGT1A1 gene variant on the bilirubin level were determined in neonates with hyperbilirubinemia.Method: The activity of G6PD was assayed by an auto-bioanalyzer. PCR and flow-through hybridization were used to detect 14 common G6PD mutations in G6PD deficient neonates. 211 G to A variation of UGT1A1 was determined by PCR and sequencing. The data of neonatal peak bilirubin was collected and analyzed retrospectively.Results: 74 cases of the 882 hyperbilirubinemia neonates were G6PD deficiency (8.39%) while 12 cases of the 585 non-hyperbilirubinemia neonates (control group) were G6PD deficiency (2.05%). The rate of G6PD deficiency in the hyperbilirubinemia group was higher than that of the control group. Moreover, the peak bilirubin in the G6PD-deficient group of hyperbilirubinemia neonates was 334.43±79.27μmol/L, higher than that of the normal G6PD group of hyperbilirubinemia neonates (300.30±68.62 μmol/L). The most common genotypes of G6PD deficiency were c.1376G>T and c.1388G>A, and the peak bilirubin of neonates with these two variants were 312.60±71.81μmol/L and 367.88±75.79 μmol/L, respectively. The bilirubin level of c.1388G>A was significantly higher than that of c.1376G>T. Among the 74 hyperbilirubinemia neonates with G6PD deficiency, 6 cases were 211 G to A homozygous mutation (bilirubin levels 369.55±84.51 μmol/L), 27 cases were 211 G to A heterozygous mutation (bilirubin levels 341.50±63.21 μmol/L), and 41 cases were wild genotypes (bilirubin levels 324.63±57.52 μmol/L). Conclusion: The rate of G6PD deficiency in hyperbilirubinemia neonates was significantly higher than that of the non-hyperbilirubinemia neonates in Chaozhou. For the hyperbilirubinemia group, neonates with G6PD deficiency had a higher bilirubin level compared to those with normal G6PD. For hyperbilirubinemia neonates with G6PD deficiency, there was a declining trend of bilirubin levels among 211 G to A homozygous mutation, heterozygous mutation, and wild genotype, but there was no significance statistically among the three groups.

Etiology analysis for full-term newborns with severe hyperbilirubinemia in eastern Guangdong

“…Among the 94 cases with UGT1A1 variants data, we found that 18 cases were UGT1A1 gene variant combined with G6PD de ciency, 10 cases were UGT1A1 gene variant combined with ABO hemolysis. Our previous study found that in the newborns with hyperbilirubinemia which due to G6PD de ciency, bilirubin level showed an increasing trend with the accumulation of UGT1A1 c.211G > A variant [5] ; Yang, et al [23] reported that the risk of neonatal severe hyperbilirubinemia increased signi cantly when ABO hemolytic neonates were combined with UGT1A1 gene mutation (especially 211A > G homozygous mutation).…”

“…General information including sex, gestational age, birth weight, admission weight, mode of delivery, feeding pattern, admission age, and treatment were collected. Diagnostic information included hemolytic disease of the newborn (ABO hemolysis and Rh hemolysis), glucose-6-phosphate dehydrogenase (G6PD) de ciency (G6PD enzyme activity ≤ 1300U/L, Co-Heath Beijing Laboratories Co., Ltd. [5] ), infection (including sepsis, pneumonia, urinary tract infection, etc. ), extravascular hemorrhage (including intracranial hematoma, scalp hematoma and other bleeding), polycythemia (venous red blood cells > 6×10 12 /L, hemoglobin > 220g/L, and hematocrit > 65%), congenital hypothyroidism (diagnosed by neonatal screening), insu cient breastfeeding (breastfeeding newborns with 10% birth weight loss after birth), breast milk jaundice, prolonged jaundice (onset in neonatal period, jaundice lasted for more than 2 weeks, bilirubin level > 150µmol/L), bilirubin encephalopathy (hyperbilirubinemia and typical clinical symptoms of nervous system), blood exchange indications (blood exchange reference standard recommended by American Academy of Pediatrics in 2004) [2] .…”

“…) and one polymorphism c.1311C > T [5]. UGT1A1 gene was ampli ed and sequenced (PE Biosystems, CT, USA) to detect c.211G > A variant (UGT1A1*6, rs4148323), which was speci cally described in our previous study [5] . 94 severe hyperbilirubinemia newborns were tested for UGT1A1*6 variant (rs4148323).…”