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Common variations in PSMD3-CSF3 and PLCB4 are associated with neutrophil count.

Human molecular genetics (2010-02-23)
Yukinori Okada, Yoichiro Kamatani, Atsushi Takahashi, Koichi Matsuda, Naoya Hosono, Hiroko Ohmiya, Yataro Daigo, Kazuhiko Yamamoto, Michiaki Kubo, Yusuke Nakamura, Naoyuki Kamatani
ABSTRACT

Neutrophils are the most abundant subtype of white blood cells (WBCs). Although the regulation of the numbers of neutrophils would have substantial clinical impacts, the studies on the variations associated with neutrophil count had not been performed further. To investigate genetic variations that regulate neutrophil count, we performed a genome-wide association study in 5771 Japanese subjects and a replication study using independent 1894 Japanese subjects. We identified two genetic loci significantly associated with neutrophil count (rs4794822 in PSMD3-CSF3 at 17q21.1, P = 6.3 x 10(-10); rs2072910 in PLCB4 at 20p12, P = 3.1 x 10(-10)). As these loci did not indicate significant associations with the counts of the other subtypes of WBCs (lymphocytes, monocytes, eosinophils and basophils), their specific associations with neutrophils were suggested. The combination of the single nucleotide polymorphisms (SNPs) in these two loci explained 1.0% of the total variance of the log-transformed values of the neutrophil count in our study populations. The subjects who were homozygous for 'neutrophil-increasing alleles' in both of the SNPs (T alleles for rs4794822 and rs2072910) had 1.17-fold (95% confidence interval: 1.10-1.24) higher neutrophil count when compared with the subjects homozygous for 'neutrophil-decreasing alleles' (C alleles for rs4794822 and rs2072910). In conclusion, our study would demonstrate the significant contribution of PSMD3-CSF3 and PLCB4 loci to the regulation of neutrophil count.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Granulocyte colony-stimulating factor human, G-CSF, recombinant, expressed in E. coli, suitable for cell culture

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