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

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 sexbased 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 0 -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/mm ). 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. Am.

Correlation between bone metastasis and thrombocytosis in pulmonary adenocarcinoma patients

“…This difference in the normal range of PLT counts between Europe and the USA, and China, must be addressed; it may be associated with differences in ethnicity and/or measurement instruments. Using pairwise comparison, Zeng et al ( 21 ) identified that the frequency of the thrombopoietin receptor (TPOR) C allele at position 550 is significantly higher in subjects with high PLT counts, and that thrombocytosis is associated with a C to A transversion at position 550 in the 5′-promoter region of TPOR ( 21 ). Therefore, the present study postulates that genetic factors may be involved in the mechanism that determines the differences in the normal range of PLT in counts in Chinese subjects versus European and American subjects.…”

Oncogenic mechanisms in myeloproliferative disorders

“…Mouse models have also shown that different diseases occur in different genetic backgrounds [81]. It would therefore seem necessary to analyse putative cytokine receptor polymorphisms [105,106] that might influence white blood cell and platelet counts or haemoglobin levels in the presence of a JAK2 V617F mutation carefully, taking the sex of the patient into account. Finally, the frequencies of various chromosomal abnormalities are high in IMF patients [98,107].…”

The Bone Marrow in Normal and Disease States

“…5-12a). EPO can reverse the effects of erythroid maturation defects [15] and also has stimulatory effects on stromal proliferation [17]. The degree and kinetics of platelet rebound observed with TPO treatment is difficult to predict, [14] with age-related [16] and probable genetic differences [17].…”