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- 2017
TNF-α基因启动子-308G/A与PPAR-γ2基因-C34G多态性的交互作用与急性胰腺炎及其严重程度的关系
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Abstract:
摘要：目的 探讨TNF-α基因启动子-308G/A与PPAR-γ2基因-C34G多态性的交互作用与急性胰腺炎(AP)及其严重程度的关系。方法 选择轻度AP(MAP)、中度AP(MSAP)和重度AP(SAP)患者各150例，以450例健康体检者作为对照组。利用聚合酶链反应(PCR)技术检测外周血白细胞TNF-α基因启动子-308G/A和PPAR-γ2基因-C34G多态性，并用DNA直接测序法验证结果。结果 -308G/A(GA)、-308G/A(AA)、-C34G(CG)和-C34G(GG)基因型频率分布在MAP组分别为24.00%、26.67%、24.00%、26.00%，在MSAP组分别为34.67%、36.67%、34.00%、36.67%，在SAP组分别为42.00%、46.00%、43.33%、46.00%，在对照组分别为14.44%、14.22%、12.89%、14.67%，基因型频率在MAP组、MSAP组、SAP组与对照组之间均有统计学差异(P均<0.01)。-308G/A(GA)和-308G/A(AA)基因型者患AP的风险均显著增加(ORMAP=2.5265，ORMSAP=6.1825，ORSAP=17.8760；ORMAP=2.5700，ORMSAP=6.4018，ORSAP=18.9034)，-C34G(CG)和-C34G(GG)基因型者患AP的风险也显著增加(ORMAP=2.6684，ORMSAP=6.7769，ORSAP=22.2072；ORMAP=2.6338，ORMSAP=6.4725，ORSAP=21.5702)。基因突变的协同分析发现，-308G/A(AA)/-C34G(GG)基因型在MAP组、MSAP组、SAP组和对照组的分布频率分别为7.33%、13.33%、20.67%和2.00%，经χ2检验各组之间均有统计学差异(P均<0.01)。-308G/A(AA)/-C34G(GG)基因型者患AP的风险显著增加(ORMAP=7.2842，ORMSAP=41.2961，ORSAP=363.9736)，-308G/A(AA)与-C34G(GG)基因型在AP发生、发展中存在正向的交互作用 (γ2MAP=2.1142，γ4MAP=2.0800，γ2MSAP=2.1087，γ4MSAP=2.0506，γ2SAP=2.1388，γ4SAP=2.0001)，另外在-308G/A(GA)和-C34G(GG)之间、-308G/A(GA)和-C34G(CG)之间及-308G/A(AA)和-C34G(CG)之间均存在正向交互作用(γ均>1)。结论 携带-308G/A(GA)、-308G/A(AA)、-C34G(CG)和-C34G(GG)基因型的个体属AP高危险人群，基因型多态性的交互作用促进了AP的发生、发展。
ABSTRACT: Objective To investigate the interaction of polymorphisms of TNF-α gene promoter -308G/A and PPAR-γ2 gene -C34G with acute pancreatitis (AP) and its severity degree. Methods Totally 150 mild acute pancreatitis(MAP), 150 moderately severe acute pancreatitis(MSAP) and 150 severe acute pancreatitis(SAP) cases were selected for this study, and 450 healthy persons as control group. The genetic polymorphisms of TNF-α gene promoter -308G/A and PPAR-γ2 gene -C34G were analyzed by the technique of PCR in peripheral blood leukocytes of above-mentioned cases and the results were verified by direct DNA sequencing method.Results The frequencies of -308G/A(GA), -308G/A(AA), -C34G(CG) and -C34G(GG) were 24.00%, 26.67%, 24.00% and 26.00% in MAP group, 34.67%, 36.67%, 34.00% and 36.67% in MSAP group, 42.00%, 46.00%, 43.33% and 46.00% in SAP group, and 14.44%, 14.22%, 12.89% and 14.67% in control group, respectively. Statistical tests showed significant difference in the frequencies among each group (all P<0.01). The risk of AP significantly increased in subjects with -308G/A(GA), genotype (ORMAP=2.6776, ORMSAP=6.6250, ORSAP=21.5147), in those with -308G/A(AA) genotype (ORMAP=2.5700, ORMSAP=6.4018, ORSAP=18.9034), in those with -C34G(CG) genotype (ORMAP=2.6684，ORMSAP=6.7769，ORSAP=22.2072), and in those with -C34G(GG) genotype (ORMAP=2.6338, ORMSAP=6.4725, ORSAP=21.5702). Combined
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