Sun Manyi, Zhang Li, Shi Songli
a Department of Gastroenterology , Tianjin Union Medicine Center & Tianjin People's Hospital , Tianjin , China.
b Department of Pathology , Tianjin Union Medicine Center & Tianjin People's Hospital , Tianjin , China.
Immunol Invest. 2016;45(3):255-70. doi: 10.3109/08820139.2016.1149191. Epub 2016 Mar 28.
Multiple environmental and genetic factors contribute to the risks of ulcerative colitis (UC) and Crohn's disease (CD). Several allelic variants have been identified in natural resistance associated macrophage protein 1 (NRAMP1) gene; however, their association with UC/CD remains conflicting. The purpose of this study was to evaluate whether NRAMP1 polymorphisms are associated with the susceptibility to UC/CD.
A meta-analysis on the association between the NRAMP1 polymorphisms and susceptibility to UC/CD was performed. Relevant studies were retrieved from the databases. After eligible data were extracted, Mantel-Haenszel statistics and random/fixed effects model were applied to calculate the pooled odds radio (OR) and 95% confidence interval (95% CI).
Seven articles containing 536 UC cases, 997 CD cases, and 1361 controls were collected. No significant association between allele 2 frequency of NRAMP1 and susceptibility to UC/CD was detected in overall population (all p > 0.05). However, increased UC/CD risk for allele 3 was observed in Caucasian population (OR = 1.27, 95% CI = 1.081.50, p = 0.04), whereas decreased UC/CD risk was detected in non-Caucasian population (OR = 0.72, 95% CI = 0.600.87, p < 0.001), under "allele 3 vs. other alleles" model. Moreover, a significant increase in CD risk for T carrier frequency of -237 C/T (OR = 0.44, 95% CI, 0.26~0.75, p = 0.003) was detected, but not 274 C/T and 1729+55del4 (TGTG) +/del.
The polymorphism of -237 C/T is related to the risk of CD; and the association of allele 3 with UC/CD risk differs in Caucasian and non-Caucasian population, which might be the potential biomarkers for clinical diagnosis of UC/CD.
多种环境和遗传因素导致溃疡性结肠炎(UC)和克罗恩病(CD)的发病风险。天然抗性相关巨噬细胞蛋白1(NRAMP1)基因中已鉴定出多个等位基因变异;然而,它们与UC/CD的关联仍存在争议。本研究旨在评估NRAMP1基因多态性是否与UC/CD易感性相关。
对NRAMP1基因多态性与UC/CD易感性之间的关联进行荟萃分析。从数据库中检索相关研究。提取合格数据后,应用Mantel-Haenszel统计量和随机/固定效应模型计算合并比值比(OR)和95%置信区间(95%CI)。
收集到7篇文章,包含536例UC病例、997例CD病例和1361例对照。在总体人群中,未检测到NRAMP1基因2等位基因频率与UC/CD易感性之间存在显著关联(所有p>0.05)。然而,在“等位基因3与其他等位基因”模型下,在白种人群中观察到等位基因3使UC/CD风险增加(OR = 1.27,95%CI = 1.081.50,p = 0.04),而在非白种人群中检测到UC/CD风险降低(OR = 0.72,95%CI = 0.600.87,p < 0.001)。此外,检测到-237 C/T的T携带者频率使CD风险显著增加(OR = 0.44,95%CI,0.26~0.75,p = 0.003),但274 C/T和1729+55del4(TGTG) +/del未显示此关联。
-237 C/T多态性与CD风险相关;等位基因3与UC/CD风险的关联在白种人和非白种人群中存在差异,这可能是UC/CD临床诊断的潜在生物标志物。