Fetal hemoglobin in sickle cell anemia: genome-wide association studies suggest a regulatory region in the 5′ olfactory receptor gene cluster

Author:

Solovieff Nadia1,Milton Jacqueline N.1,Hartley Stephen W.1,Sherva Richard2,Sebastiani Paola1,Dworkis Daniel A.2,Klings Elizabeth S.2,Farrer Lindsay A.2,Garrett Melanie E.3,Ashley-Koch Allison3,Telen Marilyn J.3,Fucharoen Supan4,Ha Shau Yin5,Li Chi-Kong6,Chui David H. K.2,Baldwin Clinton T.7,Steinberg Martin H.2

Affiliation:

1. Department of Biostatistics, Boston University School of Public Health, MA;

2. Department of Medicine, Boston University School of Medicine, MA;

3. Department of Medicine, Duke University School of Medicine, Durham, NC;

4. Centre for Research & Development of Medical Diagnostic Laboratories, Khon Kaen University, Khon Kaen, Thailand;

5. Department of Pediatrics and Adolescent Medicine, University of Hong Kong, Hong Kong, SAR, China;

6. Department of Pediatrics and Adolescent Medicine, Chinese University of Hong Kong, Hong Kong, SAR, China; and

7. Center for Human Genetics, Boston University School of Medicine, MA

Abstract

Abstract In a genome-wide association study of 848 blacks with sickle cell anemia, we identified single nucleotide polymorphisms (SNPs) associated with fetal hemoglobin concentration. The most significant SNPs in a discovery sample were tested in a replication set of 305 blacks with sickle cell anemia and in subjects with hemoglobin E or β thalassemia trait from Thailand and Hong Kong. A novel region on chromosome 11 containing olfactory receptor genes OR51B5 and OR51B6 was identified by 6 SNPs (lowest P = 4.7E−08) and validated in the replication set. An additional olfactory receptor gene, OR51B2, was identified by a novel SNP set enrichment analysis. Genome-wide association studies also validated a previously identified SNP (rs766432) in BCL11A, a gene known to affect fetal hemoglobin levels (P = 2.6E−21) and in Thailand and Hong Kong subjects. Elements within the olfactory receptor gene cluster might play a regulatory role in γ-globin gene expression.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Reference55 articles.

1. Genetic modulation of sickle cell disease and thalassemia.;Steinberg,2009

2. Genetic influences on F cells and other hematologic variables: a twin heritability study.;Garner;Blood,2000

3. Genetic architecture of hemoglobin F control.;Menzel;Curr Opin Hematol,2009

4. The cooperative study of sickle cell disease: review of study design and objectives.;Gaston;Am J Pediatr Hematol Oncol,1982

5. Fetal hemoglobin in sickle cell anemia: determinants of response to hydroxyurea. Multicenter Study of Hydroxyurea.;Steinberg;Blood,1997

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