Single-nucleotide polymorphisms of the KCNS3 gene are significantly associated with airway hyperresponsiveness.
Single-nucleotide polymorphisms of the KCNS3 gene are significantly associated with airway hyperresponsiveness.
复制标题
KCNS3 基因的单核苷酸多态性与气道高反应性显着相关。
DOI：
10.1007/s00439-005-1256-5
复制
发表时间：
2005
期刊：
影响因子：
5.3
通讯作者：
Xu,Xiping
中科院分区：
文献类型：
--
作者：
Hao,Ke;Niu,Tianhua;Xu,Xin;Fang,Zhian;Xu,Xiping
气道高反应性（AHR）是哮喘的主要临床症状和中间表型之一。最近对哮喘数量性状基因座的全基因组搜索揭示了2号染色体p-末端区域与AHR之间的显著连锁信号。因此，该区域中编码钾电压门控通道延迟整流蛋白S3（KCNS 3）的基因被认为是哮喘的位置候选者。我们在48个中国人淋巴母细胞样细胞系DNA样本中评估了KCNS 3基因的12个单核苷酸多态性（SNPs）。三个SNP被发现是多态性的，并进行了测试。从最初的连锁研究样本中收集了两组独立的病例和对照组（初始筛选组和重复组）。在初始筛选集中，两个SNP（rs 1031771和rs 1031772）显示出暗示性关联，并通过复制集进一步证实。在单SNP联合分析中，rs 1031771 G等位基因（OR = 1.42，P =0.006）和rs 1031772 T等位基因（OR = 1.40，P =0.018）与AHR的发病风险显著相关。单倍型分析也检测到显着关联（P=0.006）。我们的研究结果表明，位于KCNS 3 3′下游区域的SNPs在AHR的发病中起重要作用。
Airway hyperresponsiveness (AHR) is one of the major clinical symptoms and intermediate phenotypes of asthma. A recent genome-wide search for asthma quantitative trait loci has revealed a significant linkage signal between a p-terminal region of chromosome 2 and AHR. Thus, the gene encoding the potassium voltage-gated channel delayed-rectifier protein S3 (KCNS3) in this region is considered a positional candidate for asthma. We have evaluated a total of 12 single-nucleotide polymorphisms (SNPs) of theKCNS3gene in a validation panel of 48 lymphoblastoid cell line DNA samples of Chinese origin. Three SNPs were found to be polymorphic and were tested. Two independent sets (an initial screening set and a replication set) of cases and controls from the original linkage study sample were collected. In the initial screening set, two SNPs (rs1031771 and rs1031772) showed suggestive association and were further confirmed by the replication set. In combined single-SNP analysis, the rs1031771 G allele (odds ratio=1.42,P=0.006) and rs1031772 T allele (odds ratio=1.40,P=0.018) were associated with a significantly higher risk of AHR. Haplotype analysis also detected significant association (P=0.006). Our findings suggest that SNPs located at the 3′ downstream region ofKCNS3have a significant role in the etiology of AHR.