IL2-330G polymorphic allele is associated with decreased risk of Helicobacter pylori infection in adulthood.
We evaluated whether polymorphisms in genes coding molecules linked to the innate and adaptive immune response are associated with susceptibility to Helicobacter pylori infection. IL1B-511C-->T, IL1B-31T-->C, IL1RN allele 2, IL2-330T-->G, TNFA-307G-->A, TLR2Arg677Trp, TLR2Arg753Gln, TLR4Asp299Gly, and TLR5(392STOP) polymorphisms were determined in 541 blood donors. IL2-330T-->G allele carriers had a decreased H. pylori infection risk (OR=0.63, 95% CI=0.43-0.93) after adjustment for demographic and environmental factors. Hence, we investigated whether the polymorphism is functional by evaluating IL-2 serum concentration in 150 blood donors and 100 children. IL-2 pro-inflammatory and anti-inflammatory properties were indirectly investigated by determining serum IFN-gamma and IL-10/TGF-beta levels. The polymorphism was associated with increased mean IL-2 levels in H. pylori-positive adults (2.65 pg/mL vs. 7.78 pg/mL) and children (4.19 pg/mL vs. 8.03 pg/mL). Increased IL-2 was associated with pro-inflammatory activity in adults (IFN-gamma=18.61 pg/mL vs. 25.71 pg/mL), and with anti-inflammatory activity in children (IL-10=6.99 vs. 14.17 pg/mL, TGF-beta=45.88 vs. 93.44 pg/mL) (p<10(-3) for all). In conclusion, in the context of H. pylori infection, IL2-330 T-->G polymorphism is functional and is associated with decreased risk of infection in adults.
Queiroz
Dulciene M M
DM
Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Alfredo Balena, 190/216 - 30130-100, Belo Horizonte, Brazil. dqueiroz@medicina.ufmg.br
Saraiva
Ivan E B
IE
Rocha
Gifone A
GA
Rocha
Andreia M C
AM
Gomes
Luciana I
LI
Melo
Fabrício F
FF
Bittencourt
Paulo F S
PF
D000328:Adult; D001782:Blood Donors; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D016481:Helicobacter Infections / Q000235:genetics*; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood / Q000235:genetics* / Q000276:immunology; D008297:Male; D017354:Point Mutation; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA
C508594:IL2 protein, human; D007376:Interleukin-2; D016753:Interleukin-10; D007371:Interferon-gamma