Citrus Fruit Intake Is Associated with Lower Serum Bilirubin Concentration among Women with the UGT1A1*28 Polymorphism

UDP-glucuronosyltransferase (UGT) 1A1 glucuronidates bilirubin, estrogens, and xenobiotic compounds. The UGT1A1*28 polymorphism results in lower promoter activity due to 7 thymine-adenine (TA) repeats rather than the more common 6 TA repeats. Previously, we showed that serum bilirubin, a marker of UGT1A1 activity, was lower among individuals homozygous for the UGT1A1*28 polymorphism (7/7) when randomized to a high fruit and vegetable (F&V) diet, whereas there was no effect in individuals with the wild-type (6/6) and heterozygous (6/7) genotypes. Our objective here was to determine if we could detect genotype x diet interactions on bilirubin concentrations in an observational study. Healthy nonsmoking men (n = 146) and women (n = 147), recruited from the Seattle area, provided blood samples for genotyping and bilirubin measurements. We used multiple linear regression to assess the relationships among UGT1A1 genotype, bilirubin concentrations, and consumption of specific F&V [cruciferous vegetables, citrus fruits, and soy foods (n = 268)] based on FFQ and F&V from 6 botanical families [Cruciferae, Rosaceae, Rutaceae, Umbelliferae, Solanaceae, and Leguminosae (n = 261)] based on 3-d food records. We observed a significant interaction of UGT1A1 genotype and citrus consumption among women. Women with the 7/7 genotype who consumed 0.5 daily servings of citrus fruit or foods from the Rutaceae botanical family had 30% lower serum bilirubin than those with the same genotype who consumed less, whereas 6/6 and 6/7 genotypes did not differ by consumption (P for interaction = 0.006 and 0.03, respectively). These results suggest that citrus consumption may increase UGT1A1 activity among women with the 7/7 genotype.

Misty R. Saracino4,5, Jeannette Bigler4, Yvonne Schwarz4, Jyh-Lurn Chang4, Shiuying Li4, Lin Li4, Emily White4,5, John D. Potter4 and Johanna W. Lampe4,5,* 4 Fred Hutchinson Cancer Research Center, Seattle, WA, 98109 and 5 Department of Epidemiology, University of Washington, Seattle, WA 98195

Unbound (Free) Bilirubin (Bf): Improving the Paradigm for Evaluating Neonatal Jaundice

BACKGROUND: The serum or plasma total bilirubin concentration (BT) has long been the standard clinical laboratory test for evaluating neonatal jaundice, despite studies showing that BT correlates poorly with acute bilirubin encephalopathy (ABE) and its sequelae including death, classical kernicterus, or bilirubin-induced neurological dysfunction (BIND). The poor correlation between BT and ABE is commonly attributed to the confounding effects of comorbidities such as hemolytic diseases, prematurity, asphyxia, or infection. Mounting evidence suggests, however, that BT inherently performs poorly because it is the plasma non-protein-bound (unbound or free) bilirubin concentration (Bf), rather than BT, that is more closely associated with central nervous system bilirubin concentrations and therefore ABE and its sequelae.

CONTENT: This article reviews (1) the complex relationship between serum or plasma bilirubin measurements and ABE, (2) the history underlying the limited use of Bf in the clinical setting, (3) the peroxidase method for measuring Bf and technical and other issues involved in adapting the measurement to routine clinical use, (4) clinical experience using Bf in the management of newborn jaundice, and (5) the value of Bf measurements in research investigating bilirubin pathochemistry.

SUMMARY: Increasing evidence from clinical studies, clinical experience, and basic research investigating bilirubin neurotoxicity supports efforts to incorporate Bf expeditiously into the routine evaluation of newborn jaundice.

Division of Neonatology, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA