Association Of The Mdr1 Polymorphism In Chinese Patients With Inflammatory Bowel Disease

Purpose:To investigate the association between Multidrug resistance gene (MDR1) polymorphism (C3435T and G2677T / A) and inflammatory bowel disease(IBD) in China.Methods:With collecting the clinical date of IBD patients, the genotype of C3435T and G2677T/A was detected using polymerase chain Reaction-restriction fragment length polymorphism(RFLP-PCR) in 71 patients with IBD(include 60 UC and 11 CD) and 71 healthy controls. The controls were gender and age-matched to cases. Then we investigate the association between Multidrug resistance gene polymorphism and the UC patients who use the glucocorticoid after stratified by the respond of the glucocorticoid. We collecte the mucosa biopsy wax block of 60 UC patients,and 20 cases of colonic mucosa biopsy specimens from healthy controls with normal colonoscopy.Then using streptavidin-biotin-peroxidase method(SP) to investigate the expression of Pgp in the colon mucosaResults:(1) Clinical Analysis of UC: The ratio of male to female was 1.3:1 in 60 cases of UC. The mean age of onset was 38.7±13.0 years old and the mean duration of the disease was 3.7±4.3 years old. The peak of incidence was 20~40 years old.In the patients who had extra-intestinal manifestations, four of them(6.6%) have gall-stone,five of them(8.3%) had canker sore and one of them(1.6%) had pyoderma gangraenosum. A total of 30 cases used oral or intravenous glucocorticoid therapy, five of them (16.6%) were glucocorticoid-depedent or glucocorticoid-resistance, two of them used immunosuppressive agents azathioprine treatment. The cases of chronic relapsing(68.3%) and first onset(21.7%) were the most common,in all cases, 8.3% were chronic persistent,only 1.7% were acute fluminant type. The most of patients revealed pancolitis(41.6%),35% of patients had proctitis or proctosigmoiditis, 11.7% had extensive colitis,and 11.7% were diseased to the splenic flexure. In the active UC patients,most of the pancolitis and extensive colitis revealed severity disease, however, the left-side colitis and proctitis or proctosigmoiditis were mostly moderate severity. Disease extent is not correlated with disease clincical types. (2)Clinical Anaysis of CD: There were 11 cases of CD. The mean age of onset was 36.3±12.4 years old and the mean duration of the disease was 2.6±1.9 years old. The ratio of male to female was 1.2/1. In all the patients,one had left hemicolectomy (9.1%),two had perianal lesions(18.2%),six of them used glucocorticoid(54.5%), among the six patientsfour had used glucocorticoid and azathioprine. Disease behaviour was nonstricturing,nonpenetrating in 5 patients(45.5%),structuring in 5 patients(45.5%),and penetrating in 1 patient(9.0%). The location of most patients were terminal ileum and ileocolonic(27.2%,36.4%, respectively). (3) The genotype of MDR1 analysis: The MDR1 C3435T and G2677T/A gene distribution in line with the Hardy-Weinberg balance (P> 0.05) in the cases and controls. The genotype frequencies of CC,CT and TT of MDR1 C3435T were 38.0%,45.1% and 16.9%, respectively. The genotype frequencies of GG,GA,GT,TT,TA and AA of MDR1 G2677/A were 33.8%,25.4%,11.2%,15.5%,9.9%and 4.2%, respectively. No significant difference was observed for both MDR1 G2677T/A and C3435T polymorphisms on overall disease susceptibility for IBD patients compared to the control subjects. Both the T allele and TT genotype of the MDR1 3435 SNP were no significant difference in patients with IBD compared with healthy controls,the same as the T allele and TT genotype of the MDR1 2677 SNP.The C3435T SNP was not correlated with disease extent and disease severity of UC. The 2677TT genotype trend to be higher in the patients of sigmoiditis and proctitis(P=0.048,OR 3.375(1.01-11.279)),but there was no relationship between G2677T/A SNP and the disease severity of UC. The UC patients who received systemic glucocorticoid therapy were recruited and divided into steroid-effective colitis and steriod-dependent or steroid-refractory colitis according to the response to therapy. The genotype distribution was not statistically difference between the effective group and control group. There was no statistically difference of 3435T/2677T allele and 3435TT/2677TT genotype between steroid-effective group , steroid-dependent / steroid-refractory group and the controls.(4)The results of Pgp immunohistochemical: In the UC patients group, the positive rate of Pgp expression was 65%, while the positive rate in the control group was 55%. There was no difference between the two group(χ2=0.640,P=0.424). After stratified by the disease severity in the 37 patients with compelte case information, we found the positive rate of Pgp expression was highest in the mild severity group(80%), however it was no statistical difference(P>0.05). Conclusions:(1)In the hospitalized cases of UC, the onset is mostly middle-aged, pancolitis is the most common.The clinical type mostly is chronic relapsing.The disease extent is correlated with the disease severity in active UC. Disease behaviour of CD patients are mainly nonstricturing, nonpenetrating and structuring. While the location of most patients were terminal ileum and ileocolonic. (2) The distribution of MDR1 gene polymorphism in the IBD group and control group was found no significant difference. The genotypes of MDR1 are not associated with disease severity of UC,however,it may be effect the extent of disease, because the 2677TT genotype is correlated with sigmoiditis and proctitis. (3)We find there is no relationship between the MDR1 gene polymorphism and the respond of glucocorticoid therapy in UC patients. But as the sample is small, further study of larger sample is needed. (4) The expression of Pgp in the colon mucosa of UC patients is not different with controls. It is not associated with disease severity of UC.