The interleukin-1 RN polymorphism and Helicobacter pylori infection in the development of duodenal ulcer.
BACKGROUND
The host genetic factors that determine the clinical outcomes for Helicobacter pylori-infected individuals remain unclear.


OBJECTIVE
To elucidate the relations among interleukin-1 locus polymorphisms, and H. pylori infection in the development of duodenal ulcers.


METHODS
In a case-control study involving 168 control subjects and 147 patients with duodenal ulcer, biallelic polymorphisms of two interleukin-1 loci, IL-1B(-511) and IL-1B(+3954), as well as the penta-allelic variable number of tandem repeats of interleukin-1 receptor antagonist IL-1RN, were genotyped, and the H. pylori states of controls and patients were examined.


RESULTS
Helicobacter pylori infection, male gender and the carriage of IL-1RN*2 independently increased the risk of duodenal ulcer with odds ratios of 6.4 (95% confidence interval, 3.7-11.0), 1.9 (95% confidence interval, 1.1-3.4) and 2.7 (95% confidence interval, 1.1-6.8), respectively. Statistical analysis revealed an interaction between IL-1RN*2 and H. pylori infection with the duodenal ulcer risk conferred by the H. pylori infection substantially increased (odds ratios, 22.6; 95% confidence interval, 5.9-86.5) by the carriage of IL-1RN*2. In addition, a synergistic interaction between IL-1RN*2 and blood group O existed. The combined risk of H. pylori infection, the carriage of IL-1RN*2 and blood group O for duodenal ulcer was 27.5 (95% confidence interval, 3.1-243.6).


CONCLUSIONS
This work is the first to verify IL-1RN*2 as an independent factor that governs the development of duodenal ulcers. Our data indicate that H. pylori infection and IL-1RN*2 synergistically determine susceptibility to duodenal ulcer. The blood group phenotype is possibly a crucial determinant for the outcome of the impact of an interleukin-1 locus polymorphism on H. pylori-infected individuals.
Hsu
Ping-I
PI
Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, National Yang-Ming University, Kaohsiung, Taiwan.
Li
Chin-Ni
CN
Tseng
Hui-Hwa
HH
Lai
Kwok-Hung
KH
Hsu
Ping-Ning
PN
Lo
Gin-Ho
GH
Lo
Ching-Chu
CC
Yeh
Jeng-Jung
JJ
Ger
Luo-Ping
LP
Hsiao
Michael
M
Yamaoka
Yoshio
Y
Hwang
Il-Ran
IR
Chen
Angela
A
D000017:ABO Blood-Group System; D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D004381:Duodenal Ulcer / Q000235:genetics / Q000382:microbiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications / Q000235:genetics*; D016480:Helicobacter pylori; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012795:Sialoglycoproteins / Q000235:genetics*; D013624:Taiwan
D000017:ABO Blood-Group System; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins