The Effect Of LTA4H Rs17525495 Genotype On The Pathogenesis Of IBD

Research BackgroundInflammatory bowel disease(IBD)mainly includes Crohn's disease(CD)and ulcerative colitis(UC).Its etiology and pathogenesis have not been fully elucidated.Environment,genetics,intestinal microecology and other factors are related to each other.In the 5-LO pathway,leukotriene A4 hydrolase(LTA4H)catalyzes the conversion of LTA4 to LTB4.James Jupp et al.found in a study on IBD that the number of LTA4 H stained cells in colon biopsy tissues of patients with active inflammatory bowel disease was four times that of the healthy control group,and was accompanied by a significant increase in LTB4 and neutrophils.Through the Thousand Human Genome Project,the researchers confirmed that rs17525495 is located in the LTA4 H transcription promoter region and is a functional single nucleotide polymorphism(SNP)site whose genotype affects LTA4 H transcription.Therefore,in this study,we tried to genotype the rs17525495 gene locus in UC,CD patients and healthy people,and to study the association between this gene locus and IBD patients.Research purposes1.Investigate whether IBD is related to LTA4 H SNP rs17525495,and further screen the susceptible population of IBD from the genetic level;2.Explore the IBD treatment plan from the genetic level;Research methods1.Including 377 cases of IBD(227 cases of UC,150 cases of CD)and 700 healthy controls(HC)diagnosed in the People's Hospital of Nanchang University from January 2008 to December 2019;2.Take out paraffin biopsy specimens from patients with UC and CD,then cut three 20 um thick samples,immediately transfer to EP tube and store at-20?.Collect 2 ml of heparin anticoagulated whole blood from the healthy control group,and immediately store it in a refrigerator at 4�C;3.Use FFPE DNA kit(OMERA,USA)to extract genetic DNA from paraffin biopsy specimens of UC and CD patients as described above.DNeasy Blood &Tissue(QIAGEN,USA)was also used to extract genetic DNA from whole blood of healthy control group(HC).4.Using the ABI 7500 real-time PCR system(ABI,USA),TaqMan probe method was used to genotype SNP rs17525495 in a 20 ul reaction volume.5.Statistical analysis.Research results1.When comparing the HC and CD groups,there was a significant difference in the TT genotype.The presence of the T allele may be one of the genetic risk factors for Crohn's disease;2.In CD patients,the presence of the T allele significantly increases the proportion of patients with Crohn's disease who require glucocorticoids.In conclusionIn summary,we found that the LTA4 H rs17525495 T allele is a risk factor for CD.More importantly,there is a clear correlation between genotype and drug efficacy.The presence of the rs17525495 T allele makes CD patients more sensitive to hormone therapy.