Effect of interleukin 1 polymorphisms on gastric mucosal interleukin 1beta production in Helicobacter pylori infection.
OBJECTIVE
Although epidemiological studies suggest that interleukin (IL)-1 genetic polymorphisms are involved in Helicobacter pylori-related gastric carcinogenesis, the data are conflicting regarding the effects of these polymorphisms on IL-1beta production.


METHODS
IL-1B-511 polymorphism was genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism, and IL-1RN variable number of tandem repeats was determined by PCR. Mucosal IL-1beta levels were measured by enzyme-linked immunosorbent assay. To determine which factors influence mucosal IL-1beta levels, gastric inflammation, and atrophy, multiple regression analyses were performed.


RESULTS
We studied 117 H. pylori-infected Japanese patients. Carriers of the IL-1B-511T/T genotype or IL-1RN*2 allele had higher mucosal IL-1beta levels than noncarriers (partial regression coefficient [PRC] +/- SE), TT versus CC: 37.6 +/- 6 [antrum] and 32.1 +/- 6 [corpus] pg/mg protein (P < 0.001 for each), *1/*2 versus *1/*1: 24 +/- 8 [antrum] (P <0.01) and 36.5 +/- 7 [corpus] (P <0.001). Simultaneous carriers of IL-1B-511T/T genotype and IL-1RN*2 allele had the highest IL-1beta levels (82.9 +/- 12 [antrum] and 87.2 +/- 11 [corpus]) and showed a synergistic effect between 2 loci. The *1/*2 carriers were closely related to atrophy (PRC +/- SE; 0.87 +/- 0.4 [antrum] and 0.93 +/- 0.4 [corpus], P < 0.05), whereas being a carrier of the -511T/T genotype was related to severe gastric inflammation.


CONCLUSIONS
IL-1 genetic polymorphisms influenced H. pylori-related gastric mucosal IL-1beta levels and were related to gastric inflammation and atrophy, factors thought to be important in gastric carcinogenesis.
Hwang
Il-Ran
IR
Department of Medicine, Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas 77030, USA.
Kodama
Tadashi
T
Kikuchi
Shogo
S
Sakai
Kyoko
K
Peterson
Leif E
LE
Graham
David Y
DY
Yamaoka
Yoshio
Y
D000328:Adult; D000368:Aged; D001284:Atrophy; D015169:Colony Count, Microbial; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D016481:Helicobacter Infections / Q000235:genetics* / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000473:pathology; D020556:Neutrophil Infiltration; D011110:Polymorphism, Genetic; D013270:Stomach / Q000473:pathology
D007375:Interleukin-1