A pro-inflammatory genotype predisposes to Barrett's esophagus.
BACKGROUND
Severity of mucosal inflammation is shown to be associated with Barrett's esophagus (BE) development in animals. It has therefore been postulated that a strong pro-inflammatory host response predisposes to BE.


OBJECTIVE
To determine the impact of cytokine gene polymorphisms on the development of BE.


METHODS
The multiplex SNaPshot method was used to determine interleukin (IL)-12B (A+1188C), IL-10 (C-592A, C-819T, A-1082G), IL-8 (A-251T), IL-6 (G-174C) and IL-2 (G-330T) gene polymorphisms in 255 patients with BE and 247 patients with reflux esophagitis (RE).


RESULTS
The presence of the IL-12B C-allele, which is associated with increased IL-12p70 expression, was more frequently observed in BE than in RE patients [odds ratio (OR) 1.8; 95% confidence interval (CI) 1.2-2.7; P = 0.007). The risk of BE was increased in patients in whom the IL-12B C-allele coincided with a hiatal hernia (OR 2.9; 95% CI 1.32-6.58; P = 0.008). The IL-10(-1082) GG genotype, which is associated with higher IL-10 levels, was also associated with a decreased risk of BE when it was associated with the IL-12B C-allele, indicating IL-10-dependent down-regulation of IL-12p70 expression. A combination of the IL-12B AA genotype and the IL-10 AA or AG genotypes was associated with RE (OR 1.4; 95% CI 1.05-1.85; P = 0.011).


CONCLUSIONS
A genetic profile predisposing to a strong pro-inflammatory host response, mediated by IL-12p70 and partially dependent on IL-10, is associated with BE. This risk further increases when this genotype coincides with a hiatal hernia, suggesting that exposure to gastroesophageal reflux in the presence of a pro-inflammatory genetic background is a driving force in the development of BE.
Moons
L M G
LM
Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Postbus 2040, 3000 CA Rotterdam, the Netherlands.
Kusters
J G
JG
van Delft
J H M
JH
Kuipers
E J
EJ
Gottschalk
R
R
Geldof
H
H
Bode
W A
WA
Stoof
J
J
van Vliet
A H M
AH
Ketelslegers
H B
HB
Kleinjans
J C S
JC
Siersema
P D
PD
D000368:Aged; D001471:Barrett Esophagus / Q000235:genetics*; D016207:Cytokines / Q000235:genetics*; D004724:Endoscopy; D005260:Female; D005838:Genotype; D006551:Hernia, Hiatal / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D016753:Interleukin-10 / Q000235:genetics; D018664:Interleukin-12 / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000503:physiopathology; D011110:Polymorphism, Genetic; D044465:White People
D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D016209:Interleukin-8; D016753:Interleukin-10; D018664:Interleukin-12