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Association of the Mdr1 Polymorphism in Chinese Patients with Inflammatory Bowel Disease

Author: LuChunXia
Tutor: MeiQiao
School: Anhui Medical University,
Course: Internal Medicine
Keywords: Inflammatory bowel disease Ulcerative colitis Crohn's disease Multidrug resistance gene MDR Polymorphism
CLC: R574.62
Type: Master's thesis
Year: 2010
Downloads: 59
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Abstract

Objective To investigate the multidrug resistance gene (MDR1) polymorphisms (C3435T and G2677T / A) the clinical relevance of inflammatory bowel disease. Collected 71 cases of clinically diagnosed IBD patients (n = 60 UC and 11 CD) peripheral anticoagulant, extracted DNA using the polymerase chain reaction - restriction fragment length polymorphism method for the determination of MDR1 polymorphism. Recorded simultaneously IBD patient's medical history and test results, record the UC patients with hormone treatment response for group comparison. Control group matched for gender, age of match gastrointestinal symptoms in healthy individuals. The transfer of 60 patients diagnosed with UC patients colonoscopy the mucosal biopsy wax block, while specimens from outpatient colonoscopy to check the normal colonic mucosa of healthy controls, a total of 20 cases. Streptavidin-biotin - peroxidase (SP) method, the colonic mucosa of Pgp expression. Results of the ⑴ UC patients with clinical data analysis: 60 patients with UC males more than females, with a sex ratio of 1.3:1, average age 38.7 ± 13.0 years, 20 to 40 years for the incidence peak, the average duration of 3.7 ± 4.3 years. With intestinal manifestations: gallstones four cases (6.6%), oral ulcers in 5 cases (8.3%), gangrenous pyoderma in 1 case (1.6%). Use of oral steroids or intravenous hormone treatment of 30 patients (50%), steroid-resistant or dependent in 5 cases (16.6%), use of immunosuppressive agents azathioprine treatment in 2 cases (6.7%). The clinical types to chronic relapse (n = 41, 68.3%) and early onset (13 cases, 21.7%), chronic persistent in 5 cases (8.3%), fulminant in 1 case (1.7%). Extent of disease (25 cases, 41.6%) dominated the entire colon type, rectum / sigmoid colon in 21 cases (35%), a wide range of colon in 7 patients (11.7%), left colon in 7 patients (11.7%). Active UC full colitis and extensive colitis disease severity in patients with severe mainly left colitis patients and rectum / straight sigmoiditis the the disease severity in patients with mild main. The extent of the lesion has nothing to do with the clinical types. (2) CD patients clinical data analysis: 11 patients with CD average age 36.3 ± 12.4 years, mean disease duration 2.6 ± 1.9 years, male to female ratio 1.2:1. Lesion types to narrow, non-perforated (5 cases, 45.5%) and stenosis (5 cases, 45.5%) as the main perforation in 1 case (9.0%), 2 cases with perianal lesions (18.2%). Lesion type of ileal and colonic back the majority (27.2% and 36.4%, respectively). The line left colon resection in 1 case (9.1%). 6 patients (54.5%), use of hormone therapy, prednisone immunosuppressant azathioprine treatment of four cases (36.4%). (3) MDR1 genotype analysis: MDR1 C3435T and G2677T / A gene distribution consistent with Hardy-Weinberg equilibrium (P gt; 0.05) in the case and control groups. MDR1 C3435T genotype frequencies in the case group were 38.0% of the CC, CT type 45.1%, 16.9% of the TT type; MDR1 G2677 / A genotype frequencies were GG-33.8%, the GA type 25.4%, the GT type 11.2%, TT type 15.5%, TA-9.9%, and 4.2% of the AA type. MDR1 C3435T and G2677T / A genotype in the case group and control group no difference in the overall distribution. C3435T TT genotype and T allele frequency distribution of the IBD group and control group no significant difference in comparison G2677T / A TT genotype frequency and T allele frequency distribution in the two groups, also found no statistically significant difference . The C3435T genotype with UC extent of disease and disease severity are unrelated. G2677T / A TT genotype in the rectum / straight sigmoiditis have the clear advantage (P = 0.048, OR 3.375 (1.01 to 11.279)), but with the UC lesions severity has nothing to do. Observed and recorded systemic glucocorticoid therapy in patients with UC, glucocorticoid treatment response, effective group is divided into hormone and steroid-dependent or resistant group. More hormone-effective compared with the control group MDR1 genotype distribution was no significant difference. C3435T TT genotype and T allele frequency and G2677T / A TT genotype and T allele frequency distribution was no difference among these groups. (4) Pgp immunohistochemistry results: the group of UC cases Pgp expression positive rate of 65% (n = 39), control group Pgp expression positive rate of 55% (11 cases of), positive rate of two groups of Pgp no significant difference (Chi-square = 0.640, P = 0.424 ). Cases with complete data of 37 patients, grouped in accordance with the UC disease severity found in the UC mild Activities Group Pgp expression of the highest positive rate (80%), but compared with the control group and the the UC moderate group and the severe group, significant difference (P gt; 0.05). Conclusion (1) UC mostly young adults hospitalized cases involving the whole colon. Clinical types of chronic relapsing forms of. Active UC, the extent of disease and the severity of lesions. CD lesions to narrow non-perforated and narrow lesion majority of the ileum and colon. (2) MDR1 gene polymorphism distribution was no difference between the IBD group and the control group. Independent of each genotype with UC disease severity, but may affect the range of UC lesions, G2677T / A TT genotype and rectum / straight sigmoiditis significant correlation. (3) MDR1 gene polymorphism and UC corticosteroid treatment, but due to the small sample size, further large sample study is still necessary. (4) UC colonic mucosa Pgp expression and normal no significant difference compared to the UC lesion severity was no significant correlation with the expression of Pgp.

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