Department of Gastroenterology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
J Clin Immunol. 2011 Feb;31(1):69-73. doi: 10.1007/s10875-010-9461-y. Epub 2010 Sep 17.
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∼, 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.
已有研究表明，常见的 miRNA 单核苷酸多态性（SNP）与多种人类疾病的易感性相关。我们评估了 miRNA 前体 miRNA-196a2、miR-146a 和 miR-499 中三个 SNP（rs11614913、rs2910164 和 rs3746444）与日本人群溃疡性结肠炎（UC）风险的关联。
在 170 例 UC 患者和 403 例对照中，对 rs11614913（T>C）、rs2910164（C>G）和 rs3746444（A>G）SNP 进行了基因分型。
UC 组的 rs3746444 AG 基因型显著升高（比值比（OR）=1.51，95%可信区间（CI）=1.03-2.21，p=0.037）。rs3746444 AG 基因型与发病年龄较大有关（OR=1.70，95%CI=1.04-2.78，p=0.035），左侧结肠炎和全结肠炎（左侧结肠炎，OR=2.10，95%CI=1.12-3.94，p=0.024；全结肠炎，OR=1.81，95%CI=1.09-3.01，p=0.028，左侧结肠炎+全结肠炎，OR=1.91，95%CI=1.26-2.92，p=0.003）、住院次数较多（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）和难治性表型（OR=2.76，95%CI=1.46-5.21，p=0.002），而 rs3746444 AA 基因型与住院次数呈负相关（2∼，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）和难治性表型（OR=0.38，95%CI=0.20-0.72，p=0.003）。rs11614913 TT 基因型也与难治性表型显著相关（T/T 与 T/C+C/C，OR=2.21，95%CI=1.17-4.18，p=0.016）。
我们的结果首次提供了证据表明 rs3746444 SNP 可能影响 UC 的易感性，rs3746444 和 rs11614913 SNP 可能影响 UC 的病理生理特征。
