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A genome-wide association study of total bilirubin and cholelithiasis risk in sickle cell anemia.

Publication ,  Journal Article
Milton, JN; Sebastiani, P; Solovieff, N; Hartley, SW; Bhatnagar, P; Arking, DE; Dworkis, DA; Casella, JF; Barron-Casella, E; Bean, CJ ...
Published in: PLoS One
2012

Serum bilirubin levels have been associated with polymorphisms in the UGT1A1 promoter in normal populations and in patients with hemolytic anemias, including sickle cell anemia. When hemolysis occurs circulating heme increases, leading to elevated bilirubin levels and an increased incidence of cholelithiasis. We performed the first genome-wide association study (GWAS) of bilirubin levels and cholelithiasis risk in a discovery cohort of 1,117 sickle cell anemia patients. We found 15 single nucleotide polymorphisms (SNPs) associated with total bilirubin levels at the genome-wide significance level (p value <5 × 10(-8)). SNPs in UGT1A1, UGT1A3, UGT1A6, UGT1A8 and UGT1A10, different isoforms within the UGT1A locus, were identified (most significant rs887829, p = 9.08 × 10(-25)). All of these associations were validated in 4 independent sets of sickle cell anemia patients. We tested the association of the 15 SNPs with cholelithiasis in the discovery cohort and found a significant association (most significant p value 1.15 × 10(-4)). These results confirm that the UGT1A region is the major regulator of bilirubin metabolism in African Americans with sickle cell anemia, similar to what is observed in other ethnicities.

Duke Scholars

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2012

Volume

7

Issue

4

Start / End Page

e34741

Location

United States

Related Subject Headings

  • Risk Factors
  • Principal Component Analysis
  • Polymorphism, Single Nucleotide
  • Isoenzymes
  • Inheritance Patterns
  • Humans
  • Glucuronosyltransferase
  • Genotype
  • Genome-Wide Association Study
  • General Science & Technology
 

Citation

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Milton, J. N., Sebastiani, P., Solovieff, N., Hartley, S. W., Bhatnagar, P., Arking, D. E., … Klings, E. S. (2012). A genome-wide association study of total bilirubin and cholelithiasis risk in sickle cell anemia. PLoS One, 7(4), e34741. https://doi.org/10.1371/journal.pone.0034741
Milton, Jacqueline N., Paola Sebastiani, Nadia Solovieff, Stephen W. Hartley, Pallav Bhatnagar, Dan E. Arking, Daniel A. Dworkis, et al. “A genome-wide association study of total bilirubin and cholelithiasis risk in sickle cell anemia.PLoS One 7, no. 4 (2012): e34741. https://doi.org/10.1371/journal.pone.0034741.
Milton JN, Sebastiani P, Solovieff N, Hartley SW, Bhatnagar P, Arking DE, et al. A genome-wide association study of total bilirubin and cholelithiasis risk in sickle cell anemia. PLoS One. 2012;7(4):e34741.
Milton, Jacqueline N., et al. “A genome-wide association study of total bilirubin and cholelithiasis risk in sickle cell anemia.PLoS One, vol. 7, no. 4, 2012, p. e34741. Pubmed, doi:10.1371/journal.pone.0034741.
Milton JN, Sebastiani P, Solovieff N, Hartley SW, Bhatnagar P, Arking DE, Dworkis DA, Casella JF, Barron-Casella E, Bean CJ, Hooper WC, DeBaun MR, Garrett ME, Soldano K, Telen MJ, Ashley-Koch A, Gladwin MT, Baldwin CT, Steinberg MH, Klings ES. A genome-wide association study of total bilirubin and cholelithiasis risk in sickle cell anemia. PLoS One. 2012;7(4):e34741.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2012

Volume

7

Issue

4

Start / End Page

e34741

Location

United States

Related Subject Headings

  • Risk Factors
  • Principal Component Analysis
  • Polymorphism, Single Nucleotide
  • Isoenzymes
  • Inheritance Patterns
  • Humans
  • Glucuronosyltransferase
  • Genotype
  • Genome-Wide Association Study
  • General Science & Technology