Polymorphisms near a chromosome 6q QTL area are associated with modulation of fetal hemoglobin levels in sickle cell anemia.

D. F. Wyszynski, C. T. Baldwin, M. A. Cleves, Y. Amirault, V. G. Nolan, J. J. Farrell, A. Bisbee, Abdullah Kutlar, L. A. Farrer, M. H. Steinberg

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

In patients with sickle cell anemia, fetal hemoglobin (HbF) concentrations vary by 2 orders of magnitude. This variance may be a result of heterogeneity in gene regulatory elements; accordingly, we searched for single nucleotide polymorphisms (SNPs) that might identify this variation. More than 180 SNPs were studied in 38 genes in 280 sickle cell anemia patients. The strongest association with HbF was found with SNPs near a QTL previously localized on chromosome 6q22.3-q23.2. Initially, two SNPs were identified in intergenic portions of this QTL and were associated with about a 20% difference in percent HbF. Subsequently, we genotyped 44 additional SNPs in the genomic region between 136.1 Mb and 137.5 Mb on chromosome 6q. Twelve SNPs, associated with a 20%-30% difference in HbF concentrations, were located in the introns of four genes, PDE7B, MAP7, MAP3K5 and PEX7. In K562 cells, the p38-MAPK pathway has been associated with the activation of gamma-globin gene expression by histone deacetylase inhibitors. Haplotypes C-T-T-T in MAP7 and T-C-C in PEX7 were significantly associated with increases in concentration of HbF, both showing strong dominance. Genetic elements abutting the 6q22.3-q23.2 QTL, may harbor trans-acting elements that help modulate baseline HbF level in sickle cell anemia.

Original languageEnglish (US)
Pages (from-to)23-33
Number of pages11
JournalCellular and molecular biology (Noisy-le-Grand, France)
Volume50
Issue number1
StatePublished - Feb 1 2004
Externally publishedYes

Fingerprint

Fetal Hemoglobin
Sickle Cell Anemia
Chromosomes
Polymorphism
Single Nucleotide Polymorphism
Nucleotides
Modulation
Genes
gamma-Globins
Histone Deacetylase Inhibitors
K562 Cells
p38 Mitogen-Activated Protein Kinases
Regulator Genes
Ports and harbors
Gene expression
Introns
Haplotypes
Chemical activation
Association reactions
Gene Expression

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Wyszynski, D. F., Baldwin, C. T., Cleves, M. A., Amirault, Y., Nolan, V. G., Farrell, J. J., ... Steinberg, M. H. (2004). Polymorphisms near a chromosome 6q QTL area are associated with modulation of fetal hemoglobin levels in sickle cell anemia. Cellular and molecular biology (Noisy-le-Grand, France), 50(1), 23-33.

Polymorphisms near a chromosome 6q QTL area are associated with modulation of fetal hemoglobin levels in sickle cell anemia. / Wyszynski, D. F.; Baldwin, C. T.; Cleves, M. A.; Amirault, Y.; Nolan, V. G.; Farrell, J. J.; Bisbee, A.; Kutlar, Abdullah; Farrer, L. A.; Steinberg, M. H.

In: Cellular and molecular biology (Noisy-le-Grand, France), Vol. 50, No. 1, 01.02.2004, p. 23-33.

Research output: Contribution to journalArticle

Wyszynski, DF, Baldwin, CT, Cleves, MA, Amirault, Y, Nolan, VG, Farrell, JJ, Bisbee, A, Kutlar, A, Farrer, LA & Steinberg, MH 2004, 'Polymorphisms near a chromosome 6q QTL area are associated with modulation of fetal hemoglobin levels in sickle cell anemia.', Cellular and molecular biology (Noisy-le-Grand, France), vol. 50, no. 1, pp. 23-33.
Wyszynski, D. F. ; Baldwin, C. T. ; Cleves, M. A. ; Amirault, Y. ; Nolan, V. G. ; Farrell, J. J. ; Bisbee, A. ; Kutlar, Abdullah ; Farrer, L. A. ; Steinberg, M. H. / Polymorphisms near a chromosome 6q QTL area are associated with modulation of fetal hemoglobin levels in sickle cell anemia. In: Cellular and molecular biology (Noisy-le-Grand, France). 2004 ; Vol. 50, No. 1. pp. 23-33.
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