The Study Of The Relationship Between Gene Polymorphisms Of IL-1B-511,IL-1RN Or GNB3C825T And Gastroesophageal Reflux Disease

BackgroundGastroesophageal reflux disease(GERD) was a common disease with motilitydisorders of upper gastrointestinal tract.Multiple factors play important roles in thepathogenesis of GERD. Recent studies have shown that some genetic factors influencedthe host’s risk of GERD.However,which genetic factors influenced the risk of GERDwere still unknown. More studies on larger sample size in different regions were neededbefore reaching a definite conclusion on the role of an individual gene. The presence ofthe IL-1B511and IL-1RN may decrease the risk of GERD,because they wereassociated with increased production of IL-1β, leading to decreased gastric acidsecretion due to the destruction of parietal cells present in the stomach and thedevelopment of gastric atrophy. Another study found an association of GERD with theGNB3C825T polymorphism because of visceral hypersensitivity. The studies aboutrelationship between gene polymorphisms of IL-1B,IL-1RN or GNB3C825T andgastroesophageal reflux disease were rare in ChinaObjective1. To study the gene polymorphisms of IL-1B or IL-1RN in patients withgastroesophageal reflux disease and to analysis the relationship between the genepolymorphisms and the risk, Helicobacter pylori(Hp) infection，symptoms and theseverity at endoscopy of GERD.2. To study the gene polymorphisms of GNB3C825T in patients with gastroesophageal reflux disease（GERD） and to analysis the relationship between thegene polymorphisms and the risk, Helicobacter pylori(Hp) infection，symptoms andthe severity at endoscopy of GERD.MethodsDuring September2009to October2011, in the First Affiliated Hospital of AnhuiMedical University，154outpatients with GERD and160age-and gender-matchedunrelated healthy individuals of similar ethnicity, free from any gastrointestinalsymptoms were enrolled. Genomic DNA obtained from3~5ml of venous bloodcollected in EDTA.The gene polymorphisms of IL-1B,IL-1RN and GNB3C825T wereanalyzed through PCR-restriction fragment length polymorphism (PCR-RFLP) afterextracting the genomic DNA.Results1. The gene polymorphisms of IL-1B or IL-1RN in patients with GERD(1)No significant differences were observed between GERD patients and controlsin the gene polymorphisms of IL-1B-511(P>0.05)；(2)The IL-1RN1,2genotype and2allele were associated with higher risk of GERD than the1,1genotype and the1allele(P <0.05);(3)The IL-1B511*T/IL-1RN*1haplotype(T1) showed lower risk ofGERD(P <0.05);(4) The presence of H. pylori infection in GERD patients wasassociated with the higher rate of the IL-1B511*CT genotype (P <0.05);(5) In thepatients with RE, the IL-1B-511CC genotype and C allele were associated with lowerrisk than the TT genotype and the T allele (P <0．05).(6) The IL-1RN*1,2genotype and2allele were associated with symptom of acid reflux or heartburn.(P<0.05).(P<0.05).(7) Logistic regression analysis identified the The IL-1RN*1,2genotype as aindependent risk factor for GERD.2. The gene polymorphisms of GNB3C825T in patients with GERD(1)The GNB3C825T TT genotype and T allele were associated with higher risk ofGERD than the CC genotype and the C allele (P <0.05);(2) The presence of H. pylori infection in GERD patients was associated with the higher rate of the GNB3C825T TTgenotype and T allele (P <0.05);(3)The GNB3C825T TT genotype and T allele wereassociated with symptom of acid reflux and heartburn. P<0.05).(4) GNB3C825T TTgenotype and T allele in the patients with NERD were higher than RE (P <0．05).(5)Logistic regression analysis identified the GNB3C825T TT genotype and T allele asindependent risk factors for GERD.Conclusions1. The IL-1RN1,2genotype and2allele，GNB3C825T TT genotype and T allelewere associated with higher risk of GERD.2. The IL-1B511*T/IL-1RN*1haplotype(T1) showed lower risk of GERD.3. The presence of H. pylori infection in GERD patients was associated with thehigher rate of the IL-1B511*CT genotype, GNB3C825T TT genotype and T allele4.The IL-1B-511CC genotype, C allele and GNB3C825T TT genotype, T allelewere inversely associated the severity at endoscopy of GERD.5. The IL-1RN1,2genotype and2allele，GNB3C825T TT genotype and T allelewere associated with higher risk of acid reflux and heartburn.6. The IL-1RN1,2genotype and GNB3C825T TT genotype were two independentrisk factors for GERD.