The Study Of The Association Between NAT2 Gene Polymorphism And Ulcerative Colitis

Objective:The pathogenesy of ulcerative colitis (UC) is not yet identified. To date, researchers consider it is related with some factors, including infection, immune, nerve, heredity and so on. Now, studying about hereditary susceptibility is increasing. N-acetyltransferase2 enzyme is the important metabolic enzyme in humans. The polymorphism ofNAT2 gene cause the change of the amino acid sequence, affecting the enzymatic active. It is reported in some countries that there is some relativity between the polymorphism of NAT2 gene and and inflammatory bowel disease. But there is no relative reportin our country. We collected 75 UC patients samples and 75 control subjects, whichare Han nationality from Tianjin of China in our study. The aim of this study is toinvestigate the prevalence of the NAT2 polymorphism by PCR-RELP technique,hoping to find out the correlation between the polymorphism and UC in the Hannationality population in Tianjin of China. Using logistic regression analysis, wefurther study the genetic susceptibility under different environments in the process ofUCMethods:1. To collect the blood samples of 75 UC patients and 75 control subjects.2. To extract the blood and detect the blood routine, blood sedimentation rate, Creactive protein and so on.3. To collect the enteroscopy and pathology results of the UC patients.4. To extract and to purify the genomic DNA from the collected blood samples.5. Using PCR-RFLP technique, the NAT2 polymorphism site was screened in 75UC patients and 75 controls. 6. To analyse the clinical data, to pursue the epidemic susceptible factor.Results:Our experiment detected three mutational sites: C481T,G590A,G857A, and check theexistence of the correspond mutational alleles: M1, M2, M3. Our aim is to find out thedifferences of the allele frequency and the genotype frequency in the UC group and thecontrol group. We found the WT, M1, M2, M3 alleles and two genotypes, slow acetylator genotype and fast acetylator genotype. The differences in frequency of alleles andgenotypes were not significant(p＞0.05). But in the UCⅢgroup patients, the frequencyof M3 (857G→A) allele was 15.1%, in the control group it was only 11.3%. Thedifference was statistically significant (p＜0.05). In addition, we used the Logisticregression analysis to investigate the susceptible factors and found that the UC familymedical history, the hobby of smoked food, and the bad habit of emptying the bowels had therelationship with UC. And we found the significant differences of M3 allele between UCgroup, UCⅢgroup and the control group (p＜0.01). But we did not find thesignificant difference in the two genotypes.Conclusions:In the Han nationality population in Tianjin of China, NAT2 polymorphism maynot play a critical role in the development of UC. But in the gravis type UC patients,the frequency of M3 allele is much higher. So we have the clue that the 857G→Amutation might be related with UC. Furthermore, people who have the M3 mutationalallele may have more chance to get UC if they bare the habbit of diet at the same time.