Skip to main content
Top
Published in: Digestive Diseases and Sciences 1/2011

01-01-2011 | Original Article

Influence of MDR1 Polymorphism on H. pylori-Related Chronic Gastritis

Authors: Tomomitsu Tahara, Tomoyuki Shibata, Hiromi Yamashita, Ichiro Hirata, Tomiyasu Arisawa

Published in: Digestive Diseases and Sciences | Issue 1/2011

Login to get access

Abstract

Background

There is evidence that changes in MDR1 function and/or expression contribute to the pathogenesis of inflammatory disorders of the gastrointestinal tract.

Aims

We aimed to investigate the effect of C3435T polymorphism of the MDR1 gene on histological chronic gastritis, and on the risk of peptic ulcer diseases.

Methods

Restriction fragment length polymorphism analysis was performed for polymorphisms at C3435T in the MDR1 gene in 556 cancer-free subjects including 116 gastric and 60 duodenal ulcers, and 380 non-ulcer subjects. Gastritis scores in the antrum were assessed according to the updated Sydney system in 384 subjects.

Results

We did not find a significant association between MDR1 genotype and gastritis scores in any of the 384 subjects. However, the 3435T carrier was significantly associated with a higher degree of neutrophil infiltration in H. pylori-positive subjects (CC vs. T carrier: p = 0.0495). When the H. pylori positive subjects were divided according to generation, the 3435T carrier was significantly associated with a higher degree of neutrophil infiltration in subjects more than 65 years of age (CC vs. T carrier: p = 0.03). Also, the MDR1 3435 TT genotype was significantly associated with a higher degree of atrophy and intestinal metaplasia in the same generation (atrophy, TT vs. C carrier: p = 0.038, intestinal metaplasia, TT vs. C carrier: p = 0.016). No association was found between MDR1 genotypes and risk of peptic ulcer diseases.

Conclusions

It appears that the C3435T polymorphism of MDR1 influences H. pylori-related inflammatory conditions in the stomach, especially in older subjects.
Literature
1.
go back to reference NIH Consensus Conference. Helicobacter pylori in peptic ulcer disease. NIH Consensus Development Panel on Helicobacter pylori in Peptic Ulcer disease. JAMA. 1994;272:65–69.CrossRef NIH Consensus Conference. Helicobacter pylori in peptic ulcer disease. NIH Consensus Development Panel on Helicobacter pylori in Peptic Ulcer disease. JAMA. 1994;272:65–69.CrossRef
2.
go back to reference Uemura N, Okamoto S, Yamamoto S, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001;345:784–789.CrossRefPubMed Uemura N, Okamoto S, Yamamoto S, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 2001;345:784–789.CrossRefPubMed
3.
go back to reference Parsonnet J, Friedman GD, Vandersteen DP, et al. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med. 1991;325:1127–1131.CrossRefPubMed Parsonnet J, Friedman GD, Vandersteen DP, et al. Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med. 1991;325:1127–1131.CrossRefPubMed
4.
go back to reference Huang JQ, Sridhar S, Chen Y, Hunt RH. Meta-analysis of the relationship between Helicobacter pylori seropositivity and gastric cancer. Gastroenterology. 1998;114:1169–1179.CrossRefPubMed Huang JQ, Sridhar S, Chen Y, Hunt RH. Meta-analysis of the relationship between Helicobacter pylori seropositivity and gastric cancer. Gastroenterology. 1998;114:1169–1179.CrossRefPubMed
5.
go back to reference Blaser MJ, Parsonnet J. Parasitism by the “slow” bacterium Helicobacter pylori leads to altered gastric homeostasis and neoplasia. J Clin Invest. 1994;94:4–8.CrossRefPubMed Blaser MJ, Parsonnet J. Parasitism by the “slow” bacterium Helicobacter pylori leads to altered gastric homeostasis and neoplasia. J Clin Invest. 1994;94:4–8.CrossRefPubMed
6.
7.
go back to reference van Veen HW, Venema K, Bolhuis H, et al. Multidrug resistance mediated by a bacterial homolog of the human multidrug transporter MDR1. Proc Natl Acad Sci USA. 1996;93:10668–10672.CrossRefPubMed van Veen HW, Venema K, Bolhuis H, et al. Multidrug resistance mediated by a bacterial homolog of the human multidrug transporter MDR1. Proc Natl Acad Sci USA. 1996;93:10668–10672.CrossRefPubMed
8.
go back to reference van Veen HW, Konings WN. The ABC family of multidrug transporters in microorganisms. Biochim Biophys Acta. 1998;1365:31–36.CrossRefPubMed van Veen HW, Konings WN. The ABC family of multidrug transporters in microorganisms. Biochim Biophys Acta. 1998;1365:31–36.CrossRefPubMed
9.
go back to reference Dean M, Rzhetsky A, Allikmets R. The human ATP-binding cassette (ABC) transporter superfamily. Genome Res. 2001;11:1156–1166.CrossRefPubMed Dean M, Rzhetsky A, Allikmets R. The human ATP-binding cassette (ABC) transporter superfamily. Genome Res. 2001;11:1156–1166.CrossRefPubMed
10.
go back to reference Ambudkar SV, Dey S, Hrycyna CA, Ramachandra M, Pastan I, Gottesman MM. Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu Rev Pharmacol Toxicol. 1999;39:361–398.CrossRefPubMed Ambudkar SV, Dey S, Hrycyna CA, Ramachandra M, Pastan I, Gottesman MM. Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu Rev Pharmacol Toxicol. 1999;39:361–398.CrossRefPubMed
11.
go back to reference Ho GT, Moodie FM, Satsangi J. Multidrug resistance 1 gene (P-glycoprotein170): an important determinant in gastrointestinal disease? Gut. 2003;52:759–766.CrossRefPubMed Ho GT, Moodie FM, Satsangi J. Multidrug resistance 1 gene (P-glycoprotein170): an important determinant in gastrointestinal disease? Gut. 2003;52:759–766.CrossRefPubMed
12.
go back to reference Banner KH, Cattaneo C, Le Net JL, Popovic A, Collins D, Gale JD. Macroscopic, microscopic and biochemical characterisation of spontaneous colitis in a transgenic mouse, deficient in the multiple drug resistance 1a gene. Br J Pharmacol. 2004;143:590–598.CrossRefPubMed Banner KH, Cattaneo C, Le Net JL, Popovic A, Collins D, Gale JD. Macroscopic, microscopic and biochemical characterisation of spontaneous colitis in a transgenic mouse, deficient in the multiple drug resistance 1a gene. Br J Pharmacol. 2004;143:590–598.CrossRefPubMed
13.
go back to reference Wilk JN, Bilsborough J, Viney JL. The mdr1a−/− mouse model of spontaneous colitis: a relevant and appropriate animal model to study inflammatory bowel disease. Immunol Res. 2005;31:151–160.CrossRefPubMed Wilk JN, Bilsborough J, Viney JL. The mdr1a−/− mouse model of spontaneous colitis: a relevant and appropriate animal model to study inflammatory bowel disease. Immunol Res. 2005;31:151–160.CrossRefPubMed
14.
go back to reference Kalitsky-Szirtes J, Shayeqanpour A, Brocks DR, Piquette-Miller M. Suppression of drug-metabolizing enzymes and efflux transporters in the intestine of endotoxin-treated rats. Drug Metab Dispos. 2004;32:20–27.CrossRefPubMed Kalitsky-Szirtes J, Shayeqanpour A, Brocks DR, Piquette-Miller M. Suppression of drug-metabolizing enzymes and efflux transporters in the intestine of endotoxin-treated rats. Drug Metab Dispos. 2004;32:20–27.CrossRefPubMed
15.
go back to reference Buyse M, Radeva G, Bado A, Farinotti R. Intestinal inflammation induces adaptation of P-glycoprotein expression and activity. Biochem Pharmacol. 2005;69:1745–1754.CrossRefPubMed Buyse M, Radeva G, Bado A, Farinotti R. Intestinal inflammation induces adaptation of P-glycoprotein expression and activity. Biochem Pharmacol. 2005;69:1745–1754.CrossRefPubMed
16.
go back to reference Cascorbi I, Gerloff T, Johne A, et al. Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects. Clin Pharmacol Ther. 2001;69:169–174.CrossRefPubMed Cascorbi I, Gerloff T, Johne A, et al. Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects. Clin Pharmacol Ther. 2001;69:169–174.CrossRefPubMed
17.
go back to reference Hoffmeyer S, Burk O, von Richter O, et al. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci U S A. 2000;97:3473–3478.CrossRefPubMed Hoffmeyer S, Burk O, von Richter O, et al. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci U S A. 2000;97:3473–3478.CrossRefPubMed
18.
go back to reference Siegsmund M, Brinkmann U, Scháffeler E, et al. Association of the P-glycoprotein transporter MDR1(C3435T) polymorphism with the susceptibility to renal epithelial tumors. J Am Soc Nephrol. 2002;13:1847–1854.CrossRefPubMed Siegsmund M, Brinkmann U, Scháffeler E, et al. Association of the P-glycoprotein transporter MDR1(C3435T) polymorphism with the susceptibility to renal epithelial tumors. J Am Soc Nephrol. 2002;13:1847–1854.CrossRefPubMed
19.
go back to reference Schwab M, Schaeffeler E, Marx C, et al. Association between the C3435T MDR1 gene polymorphism and susceptibility for ulcerative colitis. Gastroenterology. 2003;124:26–33.CrossRefPubMed Schwab M, Schaeffeler E, Marx C, et al. Association between the C3435T MDR1 gene polymorphism and susceptibility for ulcerative colitis. Gastroenterology. 2003;124:26–33.CrossRefPubMed
20.
go back to reference Tahara T, Arisawa T, Shibata T, Hirata I, Nakano H. Multi-drug resistance 1 polymorphism is associated with reduced risk of gastric cancer in the Japanese population. J Gastroenterol Hepatol. 2007;22:1678–1682.CrossRefPubMed Tahara T, Arisawa T, Shibata T, Hirata I, Nakano H. Multi-drug resistance 1 polymorphism is associated with reduced risk of gastric cancer in the Japanese population. J Gastroenterol Hepatol. 2007;22:1678–1682.CrossRefPubMed
21.
go back to reference Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 1996;20:1161–1181.CrossRefPubMed Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 1996;20:1161–1181.CrossRefPubMed
22.
go back to reference Drozdzik M, Bialecka M, Mysliwiec K, Honczarenko K, Stankiewicz J, Sych Z. Polymorphism in the P-glycoprotein drug transporter MDR1 gene: a possible link between environmental and genetic factors in Parkinson’s disease. Pharmacogenetics. 2003;13:259–263.CrossRefPubMed Drozdzik M, Bialecka M, Mysliwiec K, Honczarenko K, Stankiewicz J, Sych Z. Polymorphism in the P-glycoprotein drug transporter MDR1 gene: a possible link between environmental and genetic factors in Parkinson’s disease. Pharmacogenetics. 2003;13:259–263.CrossRefPubMed
23.
go back to reference Correa P. Helicobacter pylori and gastric carcinogenesis. Am J Surg Pathol. 1995;19(Suppl 1):S37–S43.PubMed Correa P. Helicobacter pylori and gastric carcinogenesis. Am J Surg Pathol. 1995;19(Suppl 1):S37–S43.PubMed
24.
go back to reference El-Omar EM, Penman ID, Ardill JE, Chittajallu RS, Howie C, McColl KE. Helicobacter pylori infection and abnormalities of acid secretion in patients with duodenal ulcer disease. Gastroenterology. 1995;109:681–691.CrossRefPubMed El-Omar EM, Penman ID, Ardill JE, Chittajallu RS, Howie C, McColl KE. Helicobacter pylori infection and abnormalities of acid secretion in patients with duodenal ulcer disease. Gastroenterology. 1995;109:681–691.CrossRefPubMed
25.
go back to reference Lee S, Iida M, Yao T, et al. Risk of gastric cancer in patients with non-surgically treated peptic ulcer. Scand J Gastroenterol. 1990;25:1223–1226.CrossRefPubMed Lee S, Iida M, Yao T, et al. Risk of gastric cancer in patients with non-surgically treated peptic ulcer. Scand J Gastroenterol. 1990;25:1223–1226.CrossRefPubMed
26.
go back to reference Sugimoto M, Furuta T, Shirai N, et al. MDR1 C3435T polymorphism has no influence on developing Helicobacter pylori infection-related gastric cancer and peptic ulcer in Japanese. Life Sci. 2008;83:301–304.CrossRefPubMed Sugimoto M, Furuta T, Shirai N, et al. MDR1 C3435T polymorphism has no influence on developing Helicobacter pylori infection-related gastric cancer and peptic ulcer in Japanese. Life Sci. 2008;83:301–304.CrossRefPubMed
27.
go back to reference Kim RB, Leake BF, Choo EF, et al. Identification of functionally variant MDR1 alleles among European Americans and African Americans. Clin Pharmacol Ther. 2001;70:189–199.CrossRefPubMed Kim RB, Leake BF, Choo EF, et al. Identification of functionally variant MDR1 alleles among European Americans and African Americans. Clin Pharmacol Ther. 2001;70:189–199.CrossRefPubMed
28.
go back to reference Fellay J, Marzolini C, Meaden ER, et al. Response to antiretroviral treatment in HIV-1-infected individuals with allelic variants of the multidrug resistance transporter 1: a pharmacogenetics study. Lancet. 2002;359:30–36.CrossRefPubMed Fellay J, Marzolini C, Meaden ER, et al. Response to antiretroviral treatment in HIV-1-infected individuals with allelic variants of the multidrug resistance transporter 1: a pharmacogenetics study. Lancet. 2002;359:30–36.CrossRefPubMed
29.
go back to reference Hitzl M, Drescher S, van der Kuip H, et al. Fromm MF The C3435T mutation in the human MDR1 gene is associated with altered efflux of the P-glycoprotein substrate rhodamine 123 from CD56+ natural killer cells. Pharmacogenetics. 2001;11:293–298.CrossRefPubMed Hitzl M, Drescher S, van der Kuip H, et al. Fromm MF The C3435T mutation in the human MDR1 gene is associated with altered efflux of the P-glycoprotein substrate rhodamine 123 from CD56+ natural killer cells. Pharmacogenetics. 2001;11:293–298.CrossRefPubMed
30.
go back to reference Nakamura T, Sakaeda T, Horinouchi M, et al. Effect of the mutation (C3435T) at exon 26 of the MDR1 gene on expression level of MDR1 messenger ribonucleic acid in duodenal enterocytes of healthy Japanese subjects. Clin Pharmacol Ther. 2002;71:297–303.CrossRefPubMed Nakamura T, Sakaeda T, Horinouchi M, et al. Effect of the mutation (C3435T) at exon 26 of the MDR1 gene on expression level of MDR1 messenger ribonucleic acid in duodenal enterocytes of healthy Japanese subjects. Clin Pharmacol Ther. 2002;71:297–303.CrossRefPubMed
31.
go back to reference Nardone G, Rocco A, Vaira D, et al. Expression of COX-2, mPGE-synthase1, MDR-1 (P-gp), and Bcl-xL: a molecular pathway of H pylori-related gastric carcinogenesis. J Pathol. 2004;202(3):305–312.CrossRefPubMed Nardone G, Rocco A, Vaira D, et al. Expression of COX-2, mPGE-synthase1, MDR-1 (P-gp), and Bcl-xL: a molecular pathway of H pylori-related gastric carcinogenesis. J Pathol. 2004;202(3):305–312.CrossRefPubMed
32.
go back to reference Ameyaw MM, Regateiro F, Li T, et al. MDR1 pharmacogenetics: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity. Pharmacogenetics. 2001;11:217–221.CrossRefPubMed Ameyaw MM, Regateiro F, Li T, et al. MDR1 pharmacogenetics: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity. Pharmacogenetics. 2001;11:217–221.CrossRefPubMed
33.
go back to reference Sakaeda T, Nakamura T, Horinouchi M, et al. MDR1 genotype-related pharmacokinetics of digoxin after single oral administration in healthy Japanese subjects. Pharm Res. 2001;18:1400–1404.CrossRefPubMed Sakaeda T, Nakamura T, Horinouchi M, et al. MDR1 genotype-related pharmacokinetics of digoxin after single oral administration in healthy Japanese subjects. Pharm Res. 2001;18:1400–1404.CrossRefPubMed
34.
go back to reference Bernal ML, Sinues B, Fanlo A, Mayayo E. Frequency distribution of C3435T mutation in exon 26 of the MDR1 gene in a Spanish population. Ther Drug Monit. 2003;25:107–111.CrossRefPubMed Bernal ML, Sinues B, Fanlo A, Mayayo E. Frequency distribution of C3435T mutation in exon 26 of the MDR1 gene in a Spanish population. Ther Drug Monit. 2003;25:107–111.CrossRefPubMed
Metadata
Title
Influence of MDR1 Polymorphism on H. pylori-Related Chronic Gastritis
Authors
Tomomitsu Tahara
Tomoyuki Shibata
Hiromi Yamashita
Ichiro Hirata
Tomiyasu Arisawa
Publication date
01-01-2011
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 1/2011
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-010-1251-0

Other articles of this Issue 1/2011

Digestive Diseases and Sciences 1/2011 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.