胃幽门螺杆菌感染与TLR4基因G11367C、NADPH氧化酶基因His72Tyr多态性的交互作用和特发性成年骨质疏松症的关系

Relationship between the interaction of gastric helicobacter pylori infection and polymorphism of TLR4 gene G11367C and NADPH oxidase gene His72Tyr and the idiopathic osteoporosis in adults

目的探讨胃幽门螺杆菌(H.Pylori)感染与TLR4基因G11367C、NADPH氧化酶基因His72Tyr多态性的交互作用和特发性成年骨质疏松症(IOIA)的关系。方法选择我院2011年5月至2015年7月收治的IOIA患者160例,以160例健康体检者作为对照组,两组在年龄、性别、民族、籍贯和生活习惯方面无显著性差异,以上述各组患者的外周血白细胞为样本,利用PCR-RFLP技术检测了TLR4基因G11367C和NADPH氧化酶基因His72Tyr多态性。采用^(14)C-尿素呼气试验法(^(14)C-UBT)检测受检者,H.Pylori与^(14)C结合的每分钟衰变数(DPM)以判断H.Pylori感染情况。每位研究对象进行问卷调查,采用非条件Logistic分析,估算G11367C、His72Tyr多态性和H.Pylori感染与LSCC发病风险的调整比值比(OR)及95%可信区间(95%CI),并分析G11367C、His72Tyr多态性与H.Pylori感染的交互作用。结果G11367C(GC)、His72Tyr(HT)和His72Tyr(TT)基因型频率分布在IOIA组分别为70.62%、35.00%和36.25%,在对照组分别为28.12%、13.12%和13.75%,两组之间有显著差异(P均<0.01)。G11367C(GC)基因型者患IOIA的风险均显著增加(OR=6.1442),His72Tyr(HT)和His72Tyr(TT)基因型者患IOIA的风险也显著增加(OR=6.7773,OR=6.4737)。基因突变的协同分析发现G11367C(GC)/His72Tyr(TT)基因型者频率在IOIA组和对照组的分布频率分别为25.63%和3.75%,经χ~2检验在两组之间有显著性差异(P<0.01)。G11367C(GC)/His72Tyr(TT)基因型者患IOIA的风险显著增加(OR=39.5731),G11367C(GC)和His72Tyr(TT)基因型在IOIA发生、发展存在正向的交互作用(γ_2=2.0887,γ_3=1.9856),另外G11367C(GC)和His72Tyr(HT)之间也存在正向交互作用(γ>1)。100≤DPM<500和DPM≥500的H.Pylori感染者频率分布在IOIA组分别为28.75%和40.63%,在对照组分别为15.63%和11.87%,上述H.Pylori感染状况频率在IOIA组与对照组之间均有显著差异(P均<0.01)。100≤DPM<500和DPM≥500的H.Pylori感染者患IOIA的风险性均明显增高(OR=4.4463;OR=8.0238),而DPM≥500的H.Pylori感染者患LSCC的风险性则又明显高于100≤DPM<500的H.Pylori感染者(P<0.01)。H.Pylori感染与G11367C(GC)、His72Tyr(HT)和His72Tyr(TT)基因型与均有正向交互作用(γ均大于1)。结论携带G11367C(GC)、His72Tyr(HT)和His72Tyr(TT)基因型的个体属IOIA高危险人群,这些基因型和H.Pylori感染的交互作用促进了IOIA的发生、发展,应当采取根除H.Pylor或调控基因表达的措施以达到有效预防IOIA的目的。

Objective To investigate the interaction of gastric helicobacter pylori（ H. Pylori） infection and polymorphism of tolllike receptor4（ TLR4） gene G11367 C and nicotinamide adenine dinucleotide phosphate（ NADPH） oxidase gene His72Tyr in idiopathic osteoporosis in adults（ IOIA）. Methods A total of 160 IOIA cases and 160 healthy controls in our hospital from May2011 to July 2015 were selected. No significant difference between the two groups in age,gender,ethnicity,and place of birth was observed. The genetic polymorphisms of TLR4 gene G11367 C and NADPH oxidase gene His72Tyr were analyzed using PCR-RFLP in peripheral blood leukocytes from the cases. ^14C-urea breath test（^14C-UBT） was used to test ^14C disintegration per minute（ DPM） for evaluating the infection H. Pylori. Eligible participants were personally interviewed using a questionnaire.Unconditional logistic regression model and single factor analysis were performed to calculate the adjusted odds ratios（ OR） and95% confidence intervals（ 95% CI） of G11367 C and His72Tyr polymorphisms and H. Pylori infection,respectively,and to analyze the interaction between nucleotide polymorphisms and H. Pylori infection. Results The frequencies of G11367C（ GC）,His72Tyr（ HT）,and His72Tyr（ TT） were 70. 62%,35. 00%,and 36. 25% in IOIA group,and 28. 12%,13. 12%,and 13. 75%in control group,respectively. The difference between the two groups was significant（ P〈0. 01）. The risk of IOIA significantly increased in subjects with G11367C（ GC） genotype（ OR = 6. 1442）,His72Tyr（ HT） genotype（ OR = 6. 7773）,and His72Tyr（ TT） genotype（ OR = 6. 4737）. Combined analysis of the polymorphisms showed that the percentage of G11367C（ GC） /His72Tyr（ TT） in IOIA and control groups was 25. 63% and 3. 75%,respectively,with significant difference between the two groups（ P〈0. 01）. The people who carried with G11367C（ GC） /His72Tyr（ TT） had a high risk of IOIA（ OR = 39. 5731）,and statistical analysis suggested a positive interaction between G11367C（ GC） and His72Tyr（ TT） in increasing the risk of IOIA（ γ2 = 2. 0887,γ3 = 1. 9856）. Likewise,there was also positive interaction in the pathogenesis of IOIA between G11367C（ GC） and His72Tyr（ HT）（ γ〉 1）. The frequencies of 100≤DPM 500 and DPM≥500 were 28. 75% and 40. 63% in IOIA group,and 15. 63% and11. 87% in control group,respectively. The difference between the two groups was significant（ P〈0. 01）. The risk of IOIA significantly increased in subjects with 100≤DPM 〈500（ OR = 4. 4463） and in those with DPM≥500（ OR = 8. 0238）,The IOIA incidence of DPM≥500 was significantly higher than that of 100≤DPM 〈500（ P〈0. 01）. Statistical analysis suggested a positive interaction between H. Pylori infection and G11367C（ GC）,His72Tyr（ HT）,and His72Tyr（ TT） in increasing the risk of IOIA（ γ 〉1）. Conclusion These carriers of G11367C（ GC）,His72Tyr（ HT）,and His72Tyr（ TT） genotypes may have a high risk of developing IOIA. These gene genotypes can interact with H. pylori infection in the pathogenesis of IOIA. Therefore,effective prevention measures for IOIA should consider eradicating H. Pylori or regulating gene expression.