E-选择素基因多态性及血清可溶性水平与慢性HBV感染临床结局的关系

A561C and G98T polymorphisms and plasma soluble levels of E-selectin in patients with chronic HBV infection

目的:探讨E-选择素(E-selectin)基因第2号外显子G98T和第4号外显子A561C多态性及血清可溶性水平与慢性HBV感染临床结局之间的关系.方法:从外周血中提取基因组DNA,采用聚合酶链反应-限制性片段长度多态性技术(PCR-RFLP)检测367例慢性HBV感染者(其中慢性HBV携带者97例,慢性乙肝101例,肝硬化121例,肝癌48例)和281例健康对照者E-选择素基因G98T和A561C位点多态性,同时采用酶联免疫吸附实验(ELISA)检测各组可溶性E-选择素(sE-选择素)水平.结果:E-选择素A561C多态性中A/C+C/C基因型和C等位基因频率在肝硬化组与对照组相比差异有统计学意义(P=0.006,0.002).A/C+C/C基因型患肝硬化的风险是AA基因型的2.45倍(OR=2.45,95%CI:1.28-4.72).E-选择素G98T多态性中各基因型频率和等位基因频率在各病例组与对照组相比差异无统计学意义,但在肝硬化患者中,Child-pughB+C级与A级相比较,G/T+T/T基因型频率差异有统计学意义(P=0.034),G/T+T/T基因型发展到Child-pughB或C的风险是GG型的3.07倍(OR=3.07,95%CI:1.05-8.97).慢性乙肝组和肝硬化组血清sE-选择素水平明显高于对照组(P<0.01);在肝硬化组中,血清sE-选择素水平从Child-pughA级到C级明显降低(P<0.05);在各组中,C等位基因携带者血清sE-选择素水平明显高于A等位基因携带者(P<0.05).结论:E-选择素A561C基因多态性可能与慢性HBV感染后肝硬化的发生相关,并参与调控血清可溶性E-选择素的表达;E-选择素G98T基因多态性与慢性HBV感染后的临床结局无相关性,但可能与肝硬化的严重程度相关.

AIM： To investigate the association between A561C polymorphism in the exon 2 and the G98T polymorphism in the exon 4 of E-selectin gene and disease progression in a HBV-infected Chinese Hart population, and also to determine the plasma soluble E-selectin levels in these people. METHODS： Polymorphisms （Pst I for A561C and Hph I for G98T） of E-selectin gene were analyzed using polymerase chain reaction-restric tion fragment length polymorphism （PCR-RFLP） in 367 HBV carriers and 281 healthy controls. The plasma soluble E-selectin levels were measured using specific enzyme-linked immunosorbent assay （ELISA）. RESULTS： There was significant difference in frequencies of A/C＋C/C genotype and C allele in E-selectin A561C polymorphism between patients with liver cirrhosis （LC） and controls （P = 0.006 and P = 0.002）. The relative risk of LC with A/C＋C/C genotype was 2.45 times of those with A/A genotype （OR = 2.45, 95%CI： 1.28-4.72）. There was no difference in genotype and allele distribution for E-selectin G98T polymorphism between each group and controls. But in patients with LC, the frequency of G/T＋T/T genotype was of significant difference between Child＇ class A and class B plus C after the Child- Pugh classification （P = 0.034）, the relative risk of Child-pugh B or C with G/T＋T/T genotype was 3.07 times of those with G/G genotype （OR = 3.07, 95%Ch 1.05-8.97）. Plasma levels of soluble E-selectin were significantly increased in HBV carriers with chronic hepatitis （CH） and LC compared with controls （P 〈 0.01）. In the subgroup of LC, levels of soluble E-selectin were significantly decreased from Child＇ class A to class C （P 〈 0.05）. In each group, people with C allele showed higher soluble E-selectin levels than those with A allele （P 〈 0.05）. CONCLUSION： E-selectin A561C polymorphism may be associated with liver cirrhosis in patients with chronic HBV infection and affect the plasma soluble levels, and the G98T polymorphism may be related to fibrotic severity.