Influence of MDR1 polymorphism on H. pylori-related chronic gastritis.
BACKGROUND
There is evidence that changes in MDR1 function and/or expression contribute to the pathogenesis of inflammatory disorders of the gastrointestinal tract.


OBJECTIVE
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.
Tahara
Tomomitsu
T
Department of Gastroenterology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, 470-1192, Aichi, Japan. tomomiccyu@yahoo.co.jp
Shibata
Tomoyuki
T
Yamashita
Hiromi
H
Hirata
Ichiro
I
Arisawa
Tomiyasu
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000367:Age Factors; D000368:Aged; D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D005756:Gastritis / Q000208:ethnology / Q000235:genetics* / Q000382:microbiology*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D010437:Peptic Ulcer / Q000208:ethnology / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012720:Severity of Illness Index
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1
Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3473-8
10716719
Clin Pharmacol Ther. 2001 Mar;69(3):169-74
11240981
Clin Pharmacol Ther. 2001 Aug;70(2):189-99
11503014
Clin Pharmacol Ther. 2002 Apr;71(4):297-303
11956513
Annu Rev Cell Biol. 1992;8:67-113
1282354
JAMA. 1994 Jul 6;272(1):65-9
8007082
N Engl J Med. 1991 Oct 17;325(16):1127-31
1891020
Am J Surg Pathol. 1996 Oct;20(10):1161-81
8827022
Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10668-72
8855237
Br J Pharmacol. 2004 Nov;143(5):590-8
15466445
N Engl J Med. 2001 Sep 13;345(11):784-9
11556297
Gut. 2003 May;52(5):759-66
12692067
Genome Res. 2001 Jul;11(7):1156-66
11435397
Biochim Biophys Acta. 1998 Jun 10;1365(1-2):31-6
9693718
Biochem Pharmacol. 2005 Jun 15;69(12):1745-54
15885661
Gastroenterology. 1995 Sep;109(3):681-91
7657096
J Clin Invest. 1994 Jul;94(1):4-8
8040281
Pharmacogenetics. 2001 Apr;11(3):217-21
11337937
Immunol Res. 2005;31(2):151-9
15778512
J Am Soc Nephrol. 2002 Jul;13(7):1847-54
12089380
Scand J Gastroenterol. 1990 Dec;25(12):1223-6
2274743
Pharmacogenetics. 2003 May;13(5):259-63
12724617
Ther Drug Monit. 2003 Feb;25(1):107-11
12548153
Pharmacogenetics. 2001 Jun;11(4):293-8
11434506
Pharm Res. 2001 Oct;18(10):1400-4
11697464
Lancet. 2002 Jan 5;359(9300):30-6
11809184
Gastroenterology. 1998 Jun;114(6):1169-79
9609753
J Pathol. 2004 Mar;202(3):305-12
14991895
J Gastroenterol Hepatol. 2007 Oct;22(10):1678-82
17608636
Life Sci. 2008 Aug 15;83(7-8):301-4
18644389
Gastroenterology. 2003 Jan;124(1):26-33
12512026
Drug Metab Dispos. 2004 Jan;32(1):20-7
14709616
Am J Surg Pathol. 1995;19 Suppl 1:S37-43
7762738
Annu Rev Pharmacol Toxicol. 1999;39:361-98
10331089