Document Detail

Genome-wide association study identifies genetic variants influencing F-cell levels in sickle-cell patients.
MedLine Citation:
PMID:  21326311     Owner:  NLM     Status:  MEDLINE    
Fetal hemoglobin (HbF) level has emerged as an important prognostic factor in sickle-cell disease (SCD) and can be measured by the proportion of HbF-containing erythrocytes (F-cells). Recently, BCL11A (zinc-finger protein) was identified as a regulator of HbF, and the strongest association signals were observed either directly for rs766432 or for correlated single-nucleotide polymorphisms (SNPs). To identify additional independently associated genetic variants, we performed a genome-wide association study (GWAS) on the proportion of F-cells in individuals of African ancestry with SCD from the Silent Infarct Transfusion (SIT) Trial cohort. Our study not only confirms the association of rs766432 (P-value <3.32 × 10(-13)), but also identifies an independent novel intronic SNP, rs7606173, associated with F-cells (P-value <1.81 × 10(-15)). The F-cell variances explained independently by these two SNPs are ∼13% (rs7606173) and ∼11% (rs766432), whereas, together they explain ∼16%. Additionally, in men, we identify a novel locus on chromosome 17, glucagon-like peptide-2 receptor (GLP2R), associated with F-cell regulation (rs12103880; P-value <3.41 × 10(-8)). GLP2R encodes a G protein-coupled receptor and involved in proliferative and anti-apoptotic cellular responses. These findings highlight the importance of denser genetic screens and suggest further exploration of the BCL11A and GLP2R loci to gain additional insight into HbF/F-cell regulation.
Pallav Bhatnagar; Shirley Purvis; Emily Barron-Casella; Michael R DeBaun; James F Casella; Dan E Arking; Jeffrey R Keefer
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-02-17
Journal Detail:
Title:  Journal of human genetics     Volume:  56     ISSN:  1435-232X     ISO Abbreviation:  J. Hum. Genet.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-26     Completed Date:  2011-08-22     Revised Date:  2013-03-19    
Medline Journal Info:
Nlm Unique ID:  9808008     Medline TA:  J Hum Genet     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  316-23     Citation Subset:  IM    
McKusick-Nathans Institute of Genetic Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
African Continental Ancestry Group / genetics*
Anemia, Sickle Cell / genetics*
Bayes Theorem
Carrier Proteins / genetics*
Chromosomes, Human, Pair 17 / genetics*
Cohort Studies
Erythrocyte Count
Erythrocytes / metabolism*
Fetal Hemoglobin / analysis*
Genome-Wide Association Study
Haplotypes / genetics
Nuclear Proteins / genetics*
Polymorphism, Single Nucleotide / genetics
Receptors, Glucagon / genetics
Grant Support
5R01HL091759/HL/NHLBI NIH HHS; 5U01-NS042804-03/NS/NINDS NIH HHS; HHSN268200782096C//PHS HHS; U54HL090515/HL/NHLBI NIH HHS
Reg. No./Substance:
0/BCL11A protein, human; 0/Carrier Proteins; 0/Nuclear Proteins; 0/Receptors, Glucagon; 0/glucagon-like peptide-1 receptor; 9034-63-3/Fetal Hemoglobin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Mitochondrial DNA and Y-chromosomal stratification in Iran: relationship between Iran and the Arabia...
Next Document:  Hypospadias associated with hypertelorism, the mildest phenotype of Opitz syndrome.