Association of single nucleotide polymorphisms in the thrombopoietin-receptor gene, but not the thrombopoietin gene, with differences in platelet count

She Min Zeng; Jeffrey C Murray; John A Widness; Ronald G Strauss; Jerome Yankowitz

doi:10.1002/ajh.20095

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Association of single nucleotide polymorphisms in the thrombopoietin-receptor gene, but not the thrombopoietin gene, with differences in platelet count

Journal article

Peer reviewed

Association of single nucleotide polymorphisms in the thrombopoietin-receptor gene, but not the thrombopoietin gene, with differences in platelet count

She Min Zeng, Jeffrey C Murray, John A Widness, Ronald G Strauss and Jerome Yankowitz

American journal of hematology, Vol.77(1), pp.12-21

09/2004

DOI: 10.1002/ajh.20095

PMID: 15307100

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Abstract

Little is known about the mechanisms explaining the wide variation in platelet counts (PLT) and other hematologic parameters in humans. We previously showed that the sex-based difference in hematocrit was associated with nucleotide variation in the erythropoietin receptor gene (EPOR). We sought to identify new polymorphisms of the human thrombopoietin (TPO) and thrombopoietin receptor (TPOR) genes to determine any associations with blood PLT counts. We screened TPO and TPOR for polymorphisms using single-strand conformation polymorphism (SSCP) and DNA sequencing. Association of polymorphisms was studied in 304 normal subjects with low or high PLT counts. Distribution of allelic frequency was analyzed by the Chi-square statistic. Single nucleotide polymorphisms (SNPs) with two alleles were found in TPO and TPOR. The TPO SNP was a G to A transition at nucleotide 5753, and the TPOR SNP was a C to A transversion at position 550 in the 5'-promoter area. The allelic frequencies were 0.54 for G and 0.46 for A of TPO, and 0.62 for C and 0.38 for A of TPOR in a Caucasian population. The frequency of the TPOR allele "C" was significantly higher in subjects with high PLT count (>258 k/mm3) versus low PLT count (<224 k/mm3) and in males with high PLT count (>258 k/mm3) versus males with low PLT count (<212 k/mm3). In contrast, the frequency of the TPO alleles was not related to blood PLT counts. An association of TPO and TPOR allele distribution to red and white blood cell parameters was seen. These new SNPs found for the human TPO and TPOR genes help explain variations in blood PLT counts and may be useful in patient studies related to the roles of TPO and/or TPOR in disease.

Blood Cells

Gene Frequency

Humans

Middle Aged

Receptors, Thrombopoietin

Male

Proto-Oncogene Proteins - genetics

Hematologic Tests

Chi-Square Distribution

Genetic Testing - methods

Thrombopoietin - genetics

Platelet Count

Adolescent

Sex Factors

Adult

Female

Aged

Polymorphism, Single Nucleotide

Neoplasm Proteins - genetics

Receptors, Cytokine - genetics

Details

Title: Subtitle: Association of single nucleotide polymorphisms in the thrombopoietin-receptor gene, but not the thrombopoietin gene, with differences in platelet count
Creators: She Min Zeng - Department of Obstetrics and Gynecology, University of Iowa, Iowa City, Iowa 52242-1080, USA
Jeffrey C Murray
John A Widness
Ronald G Strauss
Jerome Yankowitz
Resource Type: Journal article
Publication Details: American journal of hematology, Vol.77(1), pp.12-21
DOI: 10.1002/ajh.20095
PMID: 15307100
NLM abbreviation: Am J Hematol
ISSN: 0361-8609
eISSN: 1096-8652
Publisher: United States
Grant note: R01 HD057192 / NICHD NIH HHS P01HL46925 / NHLBI NIH HHS DE08559 / NIDCR NIH HHS
Language: English
Date published: 09/2004
Academic Unit: Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pathology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Obstetrics and Gynecology; Dental Research
Record Identifier: 9984025459102771

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