天津地区胃食管反流病患者IL-1β基因多态性的研究

Association between Interleukin-1β Genes Polymorphism and Gastroesophageal Reflux Disease in Tianjin

目的:研究白细胞介素1β(IL-1β)基因多态性与胃食管反流病(GERD)发病的相关性。方法:自134例GERD患者与182例慢性胃炎患者的胃黏膜组织提取基因组DNA,采用聚合酶链反应(PCR)方法直接测定白细胞介素1受体拮抗剂基因(IL-1RN)基因型;聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法测定IL-1β-31、IL-1β-511基因型。通过快速尿素酶法、14C呼气实验及组织切片染色法检测幽门螺杆菌(Hp)感染。结果:Hp阳性率在GERD组中为32.8%,慢性胃炎对照组中为62.6%,两组差异有统计学意义(P<0.01)。IL-1RN有3种基因型,为L/L、L/2、2/2型,其出现频率在GERD组为78.0%、14.3%、7.7%,在对照组为55.4%、25.5%、19.1%。IL-1RN*2基因型较L/L型发生GERD的风险下降了近70%,OR=0.29(95%CI,0.1～0.84)。IL-1β-31位点3种基因型为T/T、C/T、C/C型,在GERD组中的频率为53.7%、29.9%、16.4%,在对照组的频率为17.6%、26.4%、56%,与T/T型比较,携带C/C基因型者GERD发生的风险下降了近90%,OR=0.1(95%CI,0.04～0.23)。IL-1β-511位点3种基因型T/T,C/T,C/C,各基因型在GERD组和对照组中分布差异无统计学意义。结论:GERD患者中Hp感染率低;IL-1β-31位点和IL-1RN基因多态性与GERD发生有关,IL-1RN*2和IL-1β-31C/C纯合子基因型是GERD的保护性因素。

Objective： To study the association between interleukin-1 （IL-1） loci polymorphisms and gastroesophageal reflux disease （GERD） in Tianjin. Methods： The gastric mucosa from 134 patients with GERD and 182 controls with chronic gastritis were collected. Genomic DNA was extracted from gastric mucosa. The polymorphisms at IL-1β-31 （C to T）, IL-1β-511 （C to T） were genotyped by PC R-RFLP, intron 2 （86-bp VNTR） of IL-1RN were genotyped by PC R. The helicobacter pylori （Hp） infection was identified by rapid urease, ^14C-breath test and giemsa-staining. Results： The positive rate of lip was 32.8% in GERD and 62.6% in control group. There was a significant difference in two groups （P〈 0.01 ）. Three kinds of polymorphism of IL-1RN were found as L/L,L/2 and 2/2. The frequencies of three types of IL-1RN in GERD patients were 78%, 14.3% and 7.7% respectively. However, the frequencies of three types of IL-1RN in controls were 55.4%,25.5% and 19.1%. IL-1RN＊2 alleles were negatively associated with GERD （OR = 0.29,95%CI,0.1-0.84）. The polymorphisms of IL-1β-31 alleles were T/T,C/T and C/C .The frequencies of three IL-1β-31 alleles in GERD patients were 53.7% ,29.9% and 16.4% ,and in controls were 17.6% ,26.4% and 56%. The IL-1β-31-C/C genotype was inversely associated with GERD （OR = 0.1,95%CI,0.04-0.23）. The IL-1β-511 alleles were T/T,C/T and C/C. No significant differences were observed between GERD patients and controls in each genotype. Conclusion： There is a lower Hp infection in the GERD patients in Tianjin population. Both IL-1β-31 and IL-1RN＊2 allele polymorphisms were inversely associated with GERD. This study provides evidence supporting the independent protective role of IL-1β-31C/C and IL-1RN＊2 allele polymorphisms against GERD.