UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Genetic variation underlying common hereditary hyperbilirubinaemia (Gilbert's syndrome) and respiratory health in the 1946 British birth cohort

Horsfall, LJ; Hardy, R; Wong, A; Kuh, D; Swallow, DM; (2014) Genetic variation underlying common hereditary hyperbilirubinaemia (Gilbert's syndrome) and respiratory health in the 1946 British birth cohort. Journal of Hepatology , 61 (6) pp. 1344-1351. 10.1016/j.jhep.2014.07.028. Green open access

[thumbnail of 1-s2.0-S0168827814005315-main.pdf]
Preview
Text
1-s2.0-S0168827814005315-main.pdf - Published Version

Download (859kB) | Preview

Abstract

BACKGROUND & AIMS: Bilirubin has potent antioxidant properties in vitro and raised serum levels have been associated with lower rates of respiratory disease. The enzyme uridine diphosphate glucuronosyltransferase polypeptide 1A1 (UGT1A1) is solely responsible for clearing bilirubin from the blood and homozygosity for seven thymine-adenine (TA) repeats in the TATA box regulatory element of the UGT1A1 gene underlies a mild hereditary unconjugated hyperbilirubinaemia (Gilbert's syndrome). Our aim was to investigate whether this genetic variation is associated with differences in respiratory health. METHODS: The relationship between the promoter genotype underlying Gilbert's syndrome (UGT1A1 rs8175347 [TA]7/7) and respiratory outcomes assessed at ages 43, 53, and 60-64 were examined in 2190 members of the 1946 British birth cohort. RESULTS: The (TA)7/7 genotype, present in 9% of the cohort, was associated with higher forced expiratory volume (FEV1) and forced vital capacity (FVC). The relationship was strongest for heavy smokers (⩾20 cigarettes per day) at age 53 with mean FEV1 409 ml higher (191 to 627; p<0.001) and mean FVC 530 ml higher (95% CI 262-798; p<0.001) for UGT1A1 (TA)7/7 Gilbert's syndrome participants than for all others, indicating a protection from the pulmonary consequences of heavy smoking. The odds of respiratory disease (chronic obstructive pulmonary disease, self-reported asthma, or prescription of respiratory drugs) were half in those with Gilbert's syndrome genotype (odds ratio 0.49 [95% CI 0.39-0.74]; p<0.001) compared to those without this genotype. CONCLUSIONS: Genetically raised unconjugated serum bilirubin is associated with higher adult respiratory function and protection from respiratory disease.

Type: Article
Title: Genetic variation underlying common hereditary hyperbilirubinaemia (Gilbert's syndrome) and respiratory health in the 1946 British birth cohort
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jhep.2014.07.028
Publisher version: http://dx.doi.org/10.1016/j.jhep.2014.07.028
Language: English
Additional information: © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. Available under CC BY-NC-ND licence (PB 15/06/2016)
Keywords: Asthma, Bilirubin, Chronic obstructive pulmonary disease, Cohort study, Polymorphism, Respiratory function, Uridine diphosphate glucuronosyltransferase, Adult, Age Factors, Asthma, Bilirubin, Cohort Studies, Female, Forced Expiratory Volume, Genetic Variation, Genotype, Gilbert Disease, Glucuronosyltransferase, Great Britain, Humans, Incidence, Lung Diseases, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive, Respiratory Function Tests, Retrospective Studies, Smoking, Vital Capacity
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Education
UCL > Provost and Vice Provost Offices > School of Education > UCL Institute of Education
UCL > Provost and Vice Provost Offices > School of Education > UCL Institute of Education > IOE - Social Research Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine > MRC Unit for Lifelong Hlth and Ageing
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Primary Care and Population Health
URI: https://discovery.ucl.ac.uk/id/eprint/1437191
Downloads since deposit
71Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item