Laboratory for Statistical Analysis, Center for Genomic Medicine, Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan.
Hum Mol Genet. 2010 May 15;19(10):2079-85. doi: 10.1093/hmg/ddq080. Epub 2010 Feb 18.
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.
中性粒细胞是白细胞（WBC）中最丰富的亚型。尽管中性粒细胞数量的调节具有重要的临床意义，但与中性粒细胞计数相关的变化的研究尚未进一步进行。为了研究调节中性粒细胞计数的遗传变异，我们在 5771 名日本受试者中进行了全基因组关联研究，并使用独立的 1894 名日本受试者进行了复制研究。我们在 17q21.1 上的 PSMD3-CSF3 中的 rs4794822 和 20p12 上的 rs2072910 处鉴定出与中性粒细胞计数显著相关的两个遗传位点（rs4794822 在 PSMD3-CSF3 中的 P = 6.3 x 10(-10)；rs2072910 在 PLCB4 中的 P = 3.1 x 10(-10)）。由于这些位点与其他 WBC 亚型（淋巴细胞、单核细胞、嗜酸性粒细胞和嗜碱性粒细胞）的计数没有显示出显著的相关性，因此提示它们与中性粒细胞有特定的相关性。这两个位点的单核苷酸多态性（SNP）的组合解释了我们研究人群中对数转换中性粒细胞计数的总方差的 1.0%。与两个 SNP 中均为“中性粒细胞增加等位基因”纯合子的受试者相比，与两个 SNP 中均为“中性粒细胞减少等位基因”（rs4794822 和 rs2072910 的 C 等位基因）纯合子的受试者的中性粒细胞计数高 1.17 倍（95%置信区间：1.10-1.24）。总之，我们的研究将表明 PSMD3-CSF3 和 PLCB4 位点对中性粒细胞计数的调节有显著贡献。
