IL1B and IL1RN polymorphic genes and Helicobacter pylori cagA strains decrease the risk of reflux esophagitis.
OBJECTIVE
Proinflammatory interleukin (IL)-1 gene polymorphisms associated with high levels of IL-1beta activity increase the risk for hypochlorhydria and distal gastric carcinoma. The aim of this study was to evaluate whether carriers of these polymorphic genes are protected against gastroesophageal reflux disease (GERD). TNFA-308 polymorphisms were also studied.


METHODS
We prospectively evaluated 385 patients without gastric cancer and peptic ulcer. Of these patients, 383 (98 with GERD and 285 controls) were successfully genotyped for all cytokines studied. The cagA status of Helicobacter pylori isolates was determined by polymerase chain reaction (PCR). IL1B-511/-31, IL1RN, and TNFA-308 polymorphisms were genotyped by PCR, PCR/restriction fragment length polymorphism, or PCR/confronting 2-pair primers. Histologic gastritis was assessed according to the updated Sydney system. The role of the proinflammatory cytokine genotypes in the genesis of GERD was evaluated before and after stratification by H. pylori status in logistic regression models controlling for confounding factors.


RESULTS
IL1B-31 (a near-complete linkage disequilibrium between polymorphism at -31 and -511 was found) and IL1RN*2 allele polymorphisms were associated with GERD. After stratification, in the group of H. pylori-positive patients, cagA-positive status, IL1B-31 polymorphic alleles, IL1RN*2 alleles, and the degree of corpus gastritis were negatively associated with GERD. In the H. pylori-negative group, IL1B-31C/C genotype was inversely associated with GERD even after adjustment for age and sex.


CONCLUSIONS
This study provides evidence supporting the independent protective role of cagA-positive H. pylori status and IL1B and ILRN allele polymorphisms against GERD.
Queiroz
Dulciene Maria Magalhães
DM
Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. dqueiroz@medicina.ufmg.br
Guerra
Juliana Becattini
JB
Rocha
Gifone Aguiar
GA
Rocha
Andreia Maria Camargos
AM
Santos
Adriana
A
De Oliveira
Adriana Gonçalves
AG
Cabral
Mônica Maria Demas Alvares
MM
Nogueira
Ana Margarida Miguel Ferreira
AM
De Oliveira
Celso Affonso
CA
D000328:Adult; D000942:Antigens, Bacterial / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics*; D005764:Gastroesophageal Reflux / Q000150:complications / Q000235:genetics* / Q000517:prevention & control; D016481:Helicobacter Infections / Q000150:complications / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012306:Risk; D012795:Sialoglycoproteins / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; C080866:cagA protein, Helicobacter pylori