The Polymorphism rs17525495 of LTA4H Is Associated with Susceptibility of Crohn's Disease instead of Intestinal Tuberculosis in a Chinese Han Population.

Zi-Qi Yu,Chuan-Zhi Zhu,Ke-Hong Zhang,Wen-Fei Wang,Xin-Chun Chen,Jian-Yong Chen

doi:10.1155/2019/9537050

Abstract

Background Because of the similarity of intestinal tuberculosis and Crohn's disease in disease phenotype, differential diagnosis has always been a clinical problem. Arachidonic acid metabolites play an important role in the inflammatory response of intestinal tuberculosis and Crohn's disease. Recent studies have shown that the polymorphism locus in the promoter region of LTA4H gene affects LTB4 expression level and the susceptibility to extrapulmonary tuberculosis. Thus, we identified a total of 148 patients with intestinal tuberculosis, 145 with Crohn's disease, and 700 normal controls in this study. Methods All the study participants were local Han people from Jiangxi Province in the past eleven years. DNA was extracted from the paraffin-embedded specimens or the whole blood. The LTA4H promoter SNP (rs17525495) was genotyped with TaqMan assay. Results The T-alleles frequency was not significantly increased in patients with intestinal tuberculosis compared with healthy control group (p=0.630; OR=1.07; 95%CI=0.81-1.41), while patients with Crohn's disease have significantly increased T allele frequency compared with healthy population (p=0.032; OR=1.34; 95%CI=1.03-1.75). During treatment, the presence of the T allele significantly increased the proportion of Crohn's patients requiring glucocorticoids (p<0.05). Conclusions The T allele of LTA4H gene SNP (rs17525495) is a risk factor for Crohn's disease instead of intestinal tuberculosis. More importantly, there may be a potential association of the different genotypes of rs17525495 with the treatment efficacy of 5-ASA and glucocorticoids in patients with Crohn's disease. The association between LTA4H polymorphism and drugs therapeutic effects might contribute to the practice of precision medicine and the prediction of clinical outcomes.

Highlights

Intestinal tuberculosis (ITB) is a chronic granulomatous inflammation caused by M. tuberculosis invading the gut [1]
We find out the Paraffin-embedded biopsy specimens of ITB and Crohn’s disease (CD) patients and cut the FFPE sample into 3 sections 20 μm thick and transfer into EP tube stored at −20∘C immediately. 2 ml of lithium heparin anticoagulated whole blood was collected from the healthy controls, at 4∘C for storage
No significant differences were found between the ITB and CD groups in terms of gender, smoking and drinking history, WBC, Hb, ESR, PPD, or disease related surgery (p>0.05)

Summary

Introduction

Intestinal tuberculosis (ITB) is a chronic granulomatous inflammation caused by M. tuberculosis invading the gut [1]. Arachidonic acid metabolites play an important role in the inflammatory response of intestinal tuberculosis and Crohn’s disease. We identified a total of 148 patients with intestinal tuberculosis, 145 with Crohn’s disease, and 700 normal controls in this study. The T-alleles frequency was not significantly increased in patients with intestinal tuberculosis compared with healthy control group (p=0.630; OR=1.07; 95%CI=0.81-1.41), while patients with Crohn’s disease have significantly increased T allele frequency compared with healthy population (p=0.032; OR=1.34; 95%CI=1.03-1.75). The T allele of LTA4H gene SNP (rs17525495) is a risk factor for Crohn’s disease instead of intestinal tuberculosis. There may be a potential association of the different genotypes of rs17525495 with the treatment efficacy of 5-ASA and glucocorticoids in patients with Crohn’s disease. The association between LTA4H polymorphism and drugs therapeutic effects might contribute to the practice of precision medicine and the prediction of clinical outcomes

Methods

Results

Conclusion