低剂量阿司匹林相关小肠出血的新型单核苷酸多态性标志物
Novel single nucleotide polymorphism markers for low dose aspirin-associated small bowel bleeding.
作者信息
Shiotani Akiko, Murao Takahisa, Fujita Yoshihiko, Fujimura Yoshinori, Sakakibara Takashi, Nishio Kazuto, Haruma Ken
机构信息
Division of Gastroenterology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki City, Okayama, Japan.
Department of Genome Biology, Kinki University Faculty of Medicine, Sayama City, Osaka, Japan.
出版信息
PLoS One. 2013 Dec 18;8(12):e84244. doi: 10.1371/journal.pone.0084244. eCollection 2013.
BACKGROUND
Aspirin-induced enteropathy is now increasingly being recognized although the pathogenesis of small intestinal damage induced by aspirin is not well understood and related risk factors have not been established.
AIM
To investigate pharmacogenomic profile of low dose aspirin (LDA)-induced small bowel bleeding.
METHODS
Genome-wide analysis of single nucleotide polymorphisms (SNPs) was performed using the Affymetrix DMET™ Plus Premier Pack. Genotypes of candidate genes associated with small bowel bleeding were determined using TaqMan SNP Genotyping Assay kits and direct sequencing.
RESULTS
In the validation study in overall 37 patients with small bowel bleeding and 400 controls, 4 of 27 identified SNPs: CYP4F11 (rs1060463) GG (p=0.003), CYP2D6 (rs28360521) GG (p=0.02), CYP24A1 (rs4809957) T allele (p=0.04), and GSTP1 (rs1695) G allele (p=0.04) were significantly more frequent in the small bowel bleeding group compared to the controls. After adjustment for significant factors, CYP2D6 (rs28360521) GG (OR 4.11, 95% CI. 1.62 -10.4) was associated with small bowel bleeding.
CONCLUSIONS
CYP4F11 and CYP2D6 SNPs may identify patients at increased risk for aspirin-induced small bowel bleeding.
背景
尽管阿司匹林所致小肠损伤的发病机制尚未完全明确，相关危险因素也未确定，但阿司匹林诱发的肠病目前越来越受到关注。
目的
研究低剂量阿司匹林（LDA）诱发小肠出血的药物基因组学特征。
方法
使用Affymetrix DMET™ Plus Premier Pack对单核苷酸多态性（SNP）进行全基因组分析。使用TaqMan SNP基因分型检测试剂盒和直接测序法确定与小肠出血相关的候选基因的基因型。
结果
在一项纳入37例小肠出血患者和400例对照的验证研究中，27个已鉴定的SNP中的4个：CYP4F11（rs1060463）GG（p = 0.003）、CYP2D6（rs28360521）GG（p = 0.02）、CYP24A1（rs4809957）T等位基因（p = 0.04）和GSTP1（rs1695）G等位基因（p = 0.04）在小肠出血组中的出现频率显著高于对照组。在对显著因素进行校正后，CYP2D6（rs28360521）GG（比值比4.11，95%可信区间1.62 - 10.4）与小肠出血相关。
结论
CYP4F11和CYP2D6的SNP可能有助于识别阿司匹林诱发小肠出血风险增加的患者。
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