Haplotypes of the IL-1 gene cluster are associated with gastroesophageal reflux disease and Barrett’s esophagus

• Published in: Human immunology Vol. 74; no. 9; pp. 1161 - 1169
• Main Authors: Izakovicova Holla, Lydie, Borilova Linhartova, Petra, Hrdlickova, Barbara, Marek, Filip, Dolina, Jiri, Rihak, Vladimir, Kala, Zdenek
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2013
• Subjects: Adult; Allergy and Immunology; Animals; Barrett Esophagus - genetics; Barrett Esophagus - immunology; Case-Control Studies; Czech Republic; Female; Gastroesophageal Reflux - genetics; Gastroesophageal Reflux - immunology; Gene Frequency; Genetic Association Studies; Genotype; Haplotypes; Humans; Interleukin-1 - genetics; Male; Middle Aged; Multigene Family - immunology; Czech Republic; EE; BE; OR; IL-1; CI; EAC; GIQLI; GAC; NERD; GU; DU; GERD; RE; SNP; DNA; HWE; LD; LES; EC; PCR; RFLP; VNTR; esophageal cancer; interleukin-1; single nucleotide polymorphism; duodenal ulcer; gastrointestinal quality of life index; reflux esophagitis; odds ratio; variable number tandem repeat; gastric ulcer; Barrett’s esophagus; restriction fragment length polymorphism; lower esophageal sphincter; gastric adenocarcinoma; deoxyribonucleic acid; Hardy–Weinberg equilibrium; adenocarcinoma of the esophagus; non-erosive reflux disease; polymerase chain reaction; linkage disequilibrium; erosive esophagitis; confidence intervals; gastroesophageal reflux disease
• ISSN: 0198-8859; 1879-1166; 1879-1166
• DOI: 10.1016/j.humimm.2013.06.026

Gastroesophageal reflux (GERD) is a one of the major public health problem that can lead to reflux esophagitis (RE), Barrett’s esophagus (BE), and esophageal adenocarcinoma (EAC). The aim of our study was to determine the impact of IL-1 gene polymorphisms on the development of GERD, RE and BE. Three hundred and thirty-three Czech patients with gastroesophageal reflux and 165 healthy controls were included in this case-control study. Four polymorphisms in the genes of the IL-1 cluster [IL-1A(-889C/T), IL-1B(−511C/T), IL-1B(+3953C/T), and IL-1RN(VNTR)] were analyzed. Significant differences were found in IL-1RN 1/2 genotype between patients with GERD/RE and controls and in IL-1B+3953 T allele between patients with BE and healthy subjects. In addition, complex analysis revealed differences in IL-1 haplotype frequencies between the groups. Specifically, the haplotype TCCL was significantly more frequent (p=0.016) in GERD patients than in controls and the haplotype CCCL more frequent (p=0.008) in RE patients than in controls. However, in patients with BE, frequency of haplotype TCTL was lower (p=0.05) and haplotypes CTCL and TCCL were higher (p=0.03 and p=0.02) in comparison with the controls. Our results suggest that IL-1 haplotypes may be associated with susceptibility to GERD, RE and BE.