長坂 光夫

79歳女。鉄欠乏性貧血と診断され鉄剤を処方されるが改善傾向が認められず、精査加療目的に紹介となった。軽度貧血と血清鉄の低値、赤沈値の上昇を認め、腹部X線で腸閉塞像、異常石灰化像は認めず、CTでは結腸の壁肥厚を認めたが石灰像は認めなかった。大腸内視鏡検査で、盲腸は青白調の浮腫状粘膜で静脈の怒張と不整形の潰瘍を認め、上行結腸から横行結腸にかけても青白調の浮腫状粘膜であった。盲腸から盲腸の潰瘍辺縁を含めて、直腸まで生検を施行した。生検の結果、盲腸の潰瘍辺縁を含めて、粘膜固有層および粘膜下層に血管周囲の線維性肥厚と間質の線維増生を認めた。また、Azan染色にて膠原線維、間質の染色を認めた。以上の検査所見から、特発性腸間膜静脈硬化症の初期病変を疑った。

BACKGROUND: 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. METHODS: The rs11614913 (T > C), rs2910164 (C > G), and rs3746444 (A > G) SNPs were genotyped in 170 UC and 403 control subjects. RESULTS: 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). CONCLUSIONS: 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.