Polymorphisms in cytokine genes and risk of Helicobacter pylori infection among Jamaican children.
BACKGROUND
Infection by Helicobacter pylori is often acquired during childhood. Recent studies suggest that inflammatory cytokines may play a role in susceptibility to, and disease phenotype caused by, H. pylori infection, but the association of host genetic variability with risk of H. pylori infection has not been studied in children.


METHODS
We investigated the relationship between the risk of H. pylori antibody positivity and cytokine gene polymorphisms among 199 two-year-old Jamaicans. H. pylori seropositivity was determined by a validated research enzyme-linked immunosorbent assay. Real-time Taqman polymerase chain reaction was used to determine variants at 17 loci in 11 cytokine genes (IL1A, IL1B, IL2, TNF, TLR4, IL4, IL6, IL10, IL10RA, IL12A and IL13). We estimated the odds ratio and the 95% confidence interval for the association of genetic polymorphisms with H. pylori seropositivity, using logistic regression.


RESULTS
Forty (20.1%) of 199 children were seropositive. Children's H. pylori seropositivity correlated highly with maternal H. pylori seropositivity (OR = 7.98, 95% CI = 1.05-60.60, p = .02). Children carrying IL1A-889T had a lower risk of H. pylori positivity, compared to those carrying -889C, with each T allele associated with 43% risk reduction (OR = 0.57, 95% CI = 0.33-0.99, p-trend = .05). No other loci we examined were associated with the risk of H. pylori seropositivity.


CONCLUSIONS
The IL1A-889 T allele, known to express a higher level of cytokine IL-1alpha, is associated with a lower risk of H. pylori infection among Jamaican children. Our finding supports the hypothesis that an upregulation of pro-inflammatory cytokines may protect against persistent H. pylori colonization.
Tseng
Fan-Chen
FC
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Rockville, Maryland 20852, USA.
Brown
Elizabeth E
EE
Maiese
Eric M
EM
Yeager
Meredith
M
Welch
Robert
R
Gold
Benjamin D
BD
Owens
Marilyn
M
Cranston
Beverly
B
Hanchard
Barrie
B
El-Omar
Emad
E
Hisada
Michie
M
D000483:Alleles; D002648:Child; D015331:Cohort Studies; D016207:Cytokines / Q000235:genetics*; D014644:Genetic Variation; D016481:Helicobacter Infections / Q000235:genetics*; D016480:Helicobacter pylori; D006801:Humans; D053582:Interleukin-1alpha / Q000235:genetics*; D007563:Jamaica; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D012698:Serologic Tests
D016207:Cytokines; C508584:IL1A protein, human; D053582:Interleukin-1alpha