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Genetic influences on serum bilirubin in American Indians: The Strong Heart Family Study

Citation

Melton, PE and Haack, K and Goring, HH and Laston, S and Umans, JG and Lee, ET and Fabsitz, RR and Devereux, RB and Best, LG and Maccluer, JW and Almasy, L and Cole, SA, Genetic influences on serum bilirubin in American Indians: The Strong Heart Family Study, American Journal of Human Biology pp. 118-125. ISSN 1042-0533 (2011) [Refereed Article]

Copyright Statement

Copyright 2010 Wiley-Liss, Inc

DOI: doi:10.1002/ajhb.21114

Abstract

Objective: To identify genetic variation influencing serum bilirubin levels in American Indians, we performed genome-wide screening and association analyses in the Strong Heart Family Study. Bilirubin is an endogenous antioxidant that has demonstrated an inverse relationship with cardiovascular disease. Genetic variation within the promoter region of uridine diphosphate glucuronosyltransferase (UGT1A1) on chromosome 2q has been associated with elevated serum bilirubin levels in European populations. However, no study has investigated the UGT1A1 promoter in American Indians.

Methods: Statistical analyses were carried out with 3,484 participants aged 14 to 93 years recruited from three geographic areas in the United States; Arizona, Oklahoma, and North and South Dakota.

Results: Variance components linkage analysis detected a quantitative trait locus (QTL) for bilirubin on chromosome 2q in the combined centers (LOD = 6.61, P = 4.24 10⁻⁶) and in Oklahoma (LOD = 5.65, P = 4.57 24 10⁻⁵). Genetic association of the UGT1A1 promoter polymorphism was significant for all geographic locations. After adjustment using conditional linkage for UGT1A1 promoter variance, the linkage signal dropped to 1.10 in the combined sample and to 3.32 (P = 0.02) in Oklahoma, indicating this polymorphism is not completely responsible for the linkage signal in American Indians. We also detected suggestive linkage signals in the Dakotas on chromosome 10p12 (LOD = 2.18) and in the combined centers (LOD = 2.24) on chromosome 10q21.

Conclusions: Replication of a serum bilirubin QTL on chromosome 2q in American Indians implicates UGT1A1 but further genotyping is warranted to identify additional causative polymorphisms. Evidence also supports a potential novel locus for bilirubin on chromosome 10.

Item Details

Item Type:Refereed Article
Keywords:Bilirubin, UGT1A1, American Indians, family study, linkage
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Gene mapping
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biological sciences
UTAS Author:Melton, PE (Dr Phillip Melton)
ID Code:141472
Year Published:2011
Web of Science® Times Cited:6
Deposited By:Menzies Institute for Medical Research
Deposited On:2020-10-22
Last Modified:2021-06-21
Downloads:0

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