PMID- 28552477
OWN - NLM
STAT- MEDLINE
DCOM- 20180326
LR  - 20181107
IS  - 1096-0961 (Electronic)
IS  - 1079-9796 (Linking)
VI  - 65
DP  - 2017 Jun
TI  - Genome-wide association study of erythrocyte density in sickle cell disease 
      patients.
PG  - 60-65
LID - S1079-9796(17)30137-7 [pii]
LID - 10.1016/j.bcmd.2017.05.005 [doi]
AB  - Deoxy-hemoglobin S polymerization into rigid fibers is the direct cause of the 
      clinical sequelae observed in sickle cell disease (SCD). The rate of 
      polymerization of sickle hemoglobin is determined primarily by intracellular 
      hemoglobin concentration, itself dependent on the amount of sickle hemoglobin and 
      on red blood cell (RBC) volume. Dense, dehydrated RBC (DRBC) are observed in SCD 
      patients, and their number correlates with hemolytic parameters and complications 
      such as renal dysfunction, leg ulcers and priapism. To identify new genes 
      involved in RBC hydration in SCD, we performed the first genome-wide association 
      study for DRBC in 374 sickle cell anemia (HbSS) patients. We did not find 
      genome-wide significant results, indicating that variants that modulate DRBC have 
      modest-to-weak effects. A secondary analysis demonstrated a nominal association 
      (P=0.003) between DRBC in SCD patients and a variant associated with mean 
      corpuscular hemoglobin concentration (MCHC) in non-anemic individuals. This 
      intronic variant controls the expression of ATP2B4, the main calcium pump in 
      erythrocytes. Our study highlights ATP2B4 as a promising target for modulation of 
      RBC hydration in SCD patients.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Ilboudo, Yann
AU  - Ilboudo Y
AD  - Faculty of Medicine, Program in Bioinformatics, Universite de Montreal, Montreal, 
      Quebec, Canada; Montreal Heart Institute, Montreal, Quebec, Canada.
FAU - Bartolucci, Pablo
AU  - Bartolucci P
AD  - Red Cell Genetic Disease Unit, Hopital Henri-Mondor, Assistance Publique-Hopitaux 
      de Paris (AP-HP), Universite Paris Est, IMRB - U955 - Equipe no 2, Creteil, 
      France.
FAU - Rivera, Alicia
AU  - Rivera A
AD  - Division of Nephrology and Vascular Biology Research Center, Beth Israel 
      Deaconess Medical Center, Boston, USA; Department of Medicine, Harvard Medical 
      School, Boston, USA.
FAU - Sedzro, Josepha-Clara
AU  - Sedzro JC
AD  - Institut de recherches cliniques de Montreal, Montreal, Quebec, Canada.
FAU - Beaudoin, Melissa
AU  - Beaudoin M
AD  - Montreal Heart Institute, Montreal, Quebec, Canada.
FAU - Trudel, Marie
AU  - Trudel M
AD  - Faculty of Medicine, Department of Medicine and Department of Biochemistry, 
      Universite de Montreal, Montreal, Quebec, Canada; Institut de recherches 
      cliniques de Montreal, Montreal, Quebec, Canada.
FAU - Alper, Seth L
AU  - Alper SL
AD  - Division of Nephrology and Vascular Biology Research Center, Beth Israel 
      Deaconess Medical Center, Boston, USA; Department of Medicine, Harvard Medical 
      School, Boston, USA.
FAU - Brugnara, Carlo
AU  - Brugnara C
AD  - Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA, USA.
FAU - Galacteros, Frederic
AU  - Galacteros F
AD  - Red Cell Genetic Disease Unit, Hopital Henri-Mondor, Assistance Publique-Hopitaux 
      de Paris (AP-HP), Universite Paris Est, IMRB - U955 - Equipe no 2, Creteil, 
      France.
FAU - Lettre, Guillaume
AU  - Lettre G
AD  - Faculty of Medicine, Program in Bioinformatics, Universite de Montreal, Montreal, 
      Quebec, Canada; Montreal Heart Institute, Montreal, Quebec, Canada. Electronic 
      address: guillaume.lettre@umontreal.ca.
LA  - eng
GR  - MOP123382/CIHR/Canada
GR  - MOP3251163/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170513
PL  - United States
TA  - Blood Cells Mol Dis
JT  - Blood cells, molecules & diseases
JID - 9509932
RN  - 0 (Hemoglobin, Sickle)
RN  - EC 3.6.1.8 (ATP2B4 protein, human)
RN  - EC 3.6.3.8 (Plasma Membrane Calcium-Transporting ATPases)
SB  - IM
MH  - Adult
MH  - Alleles
MH  - Anemia, Sickle Cell/*blood/*genetics
MH  - Erythrocyte Indices
MH  - Erythrocytes/*metabolism
MH  - Female
MH  - Genetic Variation
MH  - *Genome-Wide Association Study
MH  - Genotype
MH  - Hemoglobin, Sickle/*genetics/*metabolism
MH  - Humans
MH  - Male
MH  - Plasma Membrane Calcium-Transporting ATPases/genetics
MH  - Polymorphism, Single Nucleotide
MH  - Quantitative Trait Loci
MH  - Young Adult
OTO - NOTNLM
OT  - ATP2B4
OT  - Dense red blood cells
OT  - GWAS
OT  - Genetic association study
OT  - Sickle cell disease
EDAT- 2017/05/30 06:00
MHDA- 2018/03/27 06:00
CRDT- 2017/05/30 06:00
PHST- 2017/03/25 00:00 [received]
PHST- 2017/05/10 00:00 [revised]
PHST- 2017/05/10 00:00 [accepted]
PHST- 2017/05/30 06:00 [pubmed]
PHST- 2018/03/27 06:00 [medline]
PHST- 2017/05/30 06:00 [entrez]
AID - S1079-9796(17)30137-7 [pii]
AID - 10.1016/j.bcmd.2017.05.005 [doi]
PST - ppublish
SO  - Blood Cells Mol Dis. 2017 Jun;65:60-65. doi: 10.1016/j.bcmd.2017.05.005. Epub 
      2017 May 13.