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

被引：115

作者：

Solovieff, Nadia ^{[2
]}

Milton, Jacqueline N. ^{[2
]}

Hartley, Stephen W. ^{[2
]}

Sherva, Richard

Sebastiani, Paola ^{[2
]}

Dworkis, Daniel A.

Klings, Elizabeth S.

Farrer, Lindsay A.

Garrett, Melanie E. ^{[3
]}

Ashley-Koch, Allison ^{[3
]}

Telen, Marilyn J. ^{[3
]}

Fucharoen, Supan ^{[4
]}

Ha, Shau Yin ^{[5
]}

Li, Chi-Kong ^{[6
]}

Chui, David H. K.

Baldwin, Clinton T. ^{[7
]}

Steinberg, Martin H. ^{[1
]}

机构：

[1] Boston Univ, Sch Med, Boston Med Ctr, Dept Med, Boston, MA 02118 USA

[2] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA

[3] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA

[4] Khon Kaen Univ, Ctr Res & Dev, Med Diagnost Labs, Khon Kaen, Thailand

[5] Univ Hong Kong, Dept Pediat & Adolescent Med, Hong Kong, Hong Kong, Peoples R China

[6] Chinese Univ Hong Kong, Dept Pediat & Adolescent Med, Hong Kong, Hong Kong, Peoples R China

[7] Boston Univ, Sch Med, Ctr Human Genet, Boston, MA 02118 USA

来源：

BLOOD | 2010年 / 115卷 / 09期

基金：

美国国家卫生研究院;

关键词：

BETA-GLOBIN LOCUS; OPEN CHROMATIN-STRUCTURE; SEQUENCE ALIGNMENTS; ERYTHROID-CELLS; PULMONARY-HYPERTENSION; THALASSEMIA PATIENTS; F-CELLS; DISEASE; MOUSE; EXPRESSION;

D O I：

10.1182/blood-2009-08-239517

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 beta 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 gamma-globin gene expression. (Blood. 2010;115:1815-1822)

引用

页码：1815 / 1822

页数：8

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