Association Study of Common Genetic Variants in Pre-microRNAs in Patients with Ulcerative Colitis
Association Study of Common Genetic Variants in Pre-microRNAs in Patients with Ulcerative Colitis
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DOI：
10.1007/s10875-010-9461-y
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发表时间：
2011-01-01
影响因子：
9.1
通讯作者：
Arisawa, Tomiyasu
中科院分区：
文献类型：
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作者：
Okubo, Masaaki;Tahara, Tomomitsu;Arisawa, Tomiyasu
MicroRNAs(MiRNA)中常见的单核苷酸多态(SNPs)已被证明与多种人类疾病的易感性有关。我们在日本人群中评估了miR-196a2、miR-146a和miR-499前miRNAs中的三个SNP(rs11614913、rs2910164和rs3746444)与溃疡性结肠炎(UC)风险的关系。在170名UC和403名对照受试者中，rs11614913(T>；C)、rs2910164(C>；G)和rs3746444(A>；G)SNP的基因分型显著高于UC组(优势比(OR)=1.51，95%=1.03-2.21，P=0.037)。AG基因型与高龄(OR=1.7，95%CI=1.0 4~2.78，p=0.035)、左侧结肠炎(左侧结肠炎，OR=2.10，95%CI=1.12~3.94，p=0.024；左侧结肠炎+全结肠炎，OR=1.91，95%CI=1.26~2.92，P=0.003)，住院次数多(OR=2.63，95%CI=1.22~5.69，P=0.017)，激素依赖(OR=2.63，95%CI=1.27~5.44，P=0.014)，难治表型(OR=2.76，P=0.014)。Rs3746444AA型与住院次数(2次相似，OR=0.36，95%CI=0.17~0.79，p=0.012)、激素依赖(OR=0.42，95%CI=0.21~0.88，p=0.021)、难治表型(OR=0.38，95%CI=0.20~0.72，p=0.003)呈负相关。Rs1161913TT型与T/C+C/C型相比具有更高的难治表型风险(OR=2.21，95%CI=1.17~4.18，p=0.016)，首次证实rs3746444SNP可能影响UC的易感性，rs3746444和rs11614913 SNPs可能影响UC的病理生理特征。
Common single-nucleotide polymorphisms (SNPs) in microRNAs (miRNA) have been shown to be associated with susceptibility to several human diseases. We evaluated the associations of three SNPs (rs11614913, rs2910164, and rs3746444) in pre-miRNAs (miR-196a2, miR-146a, and miR-499) with the risk of ulcerative colitis (UC) in a Japanese population.The rs11614913 (T > C), rs2910164 (C > G), and rs3746444 (A > G) SNPs were genotyped in 170 UC and 403 control subjects.The rs3746444 AG genotype was significantly higher among the UC group (odds ratio (OR) = 1.51, 95% CI = 1.03-2.21, p = 0.037). The rs3746444 AG genotype was associated with onset at an older age (OR = 1.70, 95% CI = 1.04-2.78, p = 0.035), left-sided colitis and pancolitis (left-sided colitis, OR = 2.10, 95% CI = 1.12-3.94, p = 0.024; pancolitis, OR = 1.81, 95% CI = 1.09-3.01, p = 0.028, left-sided colitis + pancolitis, OR = 1.91, 95% CI = 1.26-2.92, p = 0.003), higher number of times hospitalized (OR = 2.63, 95% CI = 1.22-5.69, p = 0.017), steroid dependence (OR = 2.63, 95% CI = 1.27-5.44, p = 0.014), and refractory phenotypes (OR = 2.76, 95% CI = 1.46-5.21, p = 0.002) while the rs3746444 AA genotype was inversely associated with the number of times hospitalized (2 similar to, OR = 0.36, 95% CI = 0.17-0.79, p = 0.012), steroid dependence (OR = 0.42, 95% CI = 0.21-0.88, p = 0.021), and refractory phenotypes (OR = 0.38, 95% CI = 0.20-0.72, p = 0.003). The rs1161913 TT genotype also held a significantly higher risk of refractory phenotype (T/T vs. T/C + C/C, OR = 2.21, 95% CI = 1.17-4.18, p = 0.016).Our results provided the first evidence that rs3746444 SNP may influence the susceptibility to UC, and both rs3746444 and rs11614913 SNPs may influence the pathophysiological features of UC.