Interaction between polymorphisms of TLR4 gene G11367C in 3' untranslated region and IκB-α Hae III in acute pancreatitis and the degree of severity

Abstract

To investigate the interaction between polymorphism of Toll-like receptor 4 (TLR4) gene G11367C in 3' untranslated region (UTR) and inhibitor of nuclear factor kappaB (IκB)-α Hae III in acute pancreatitis (AP) and the degree of severity. A total of 450 patients with confirmed AP (AP group), who came from the First Affiliated Hospital of Xinxiang Medical College from May 2013 to June 2015, were divided into a mild AP subgroup (MAP subgroup), a moderately severe AP (MSAP subgroup), and a severe acute AP (SAP subgroup) (n=150 in each group). One hundred fifty healthy persons were served as a control group. There was no significant difference in age, gender, ethnicity and birthplace among all groups. The genetic polymorphisms of TLR4 gene G11367C in 3' untranslated region and IκB-α HaeIII were analyzed by polymerase chain reaction (PCR). Eligible participants were personally interviewed by a questionnaire. Unconditional logistic regression model and single factor analysis were performed to calculate the adjusted odds ratios (OR) and 95% confidence intervals (95% CI) of G11367C and IκB-α HaeIII polymorphisms, respectively. The interaction of nucleotide polymorphisms was analyzed. The frequencies of G11367C (GC), IκB-α HaeIII (AG) and IκB-α HaeIII (GG) were 69.56%, 33.78% and 36.22% in the AP group; 49.33%, 24.67% and 26.00% in the MAP subgroup; 70.67%, 34.67% and 36.67% in the MSAP subgroup; 88.67%, 42.00% and 46.00% in the SAP subgroup and 26.67%, 14.00% and 14.67% in the control group, respectively. There was significant difference in the frequencies betweenc the AP group and the control group, or among each AP subgroup (all P<0.01). The risk of AP was significantly increased in the subjects with G11367C (GC) genotype (ORAP=6.2828, ORMAP=2.6776, ORMSAP=6.6250, ORSAP=21.5147), which was also increased in those with IκB-α HaeIII (AG) genotype (ORAP=5.7369, ORMAP=2.5277, ORMSAP=6.1824, ORSAP=17.8572) and in those with IκB-α HaeIII (GG) genotype (ORAP=5.8724, ORMAP=2.5902, ORMSAP=6.4027, ORSAP=18.9022). The combined analysis of the polymorphisms showed that the percentage of G11367C (GC)/ IκB-α HaeIII (GG) in the AP group, the MAP subgroup, the MSAP subgroup, the SAP subgroup and the control groups was 26.44%, 12.67%, 26.00%, 40.67% and 4.00%, respectively, with significant difference in the frequency among all groups (all P<0.01). The people who carried with Pro12Ala (AA)/Pro198Leu (LL) had a high risk of AP (ORAP=30.1314, ORMAP=6.7612, ORMSAP=39.5000, ORSAP=401.5833), and the statistical analysis suggested a positive interaction between Pro12Ala (AA) and Pro198Leu (LL) in increasing the risk of AP (All γ>1). Similarly, there were also positive interactions in the pathogenesis of AP between G11367C (GC) and IκB-α HaeIII (AG) (All γ>1). These carriers of G11367C(GC), IκB-α Hae III(AG) and IκB-α HaeIII (GG) genotypes may have a high risk of AP occurency, and there are significant interactions between genetic polymorphisms of G11367C and IκB-α Hae III, which increaes the risk of the occurrence and development of AP.