重型乙型肝炎患者MBP基因突变对白细胞介素10水平及预后的影响

Influence of mutations in mannose binding protein gene on interleukin-10 production and the prognosis of patients with severe hepatitis B

目的探讨重型乙型肝炎患者甘露糖结合蛋白(MBP)基因突变对白细胞介素10(IL-10)水平及预后的影响。方法采用基因扩增和DNA测序方法检测了68例重型乙肝患者MBP基因第一外显子的DNA序列,然后与GeneBank中参照序列进行比较分析。用酶联免疫吸附法检测其血清IL-10水平,并以40例健康人作对照。计算患者3个月生存率。结果该组重型乙肝人群中MBP基因仅存在密码子54突变,而无密码子52、57突变。密码子54突变率为36.76%(25/68)。突变者组IL-10水平为(38.92±6.84)ng/L,未突变组IL-10水平为(55.75±9.71)ng/L。二者比较差异有统计学意义(t=8.35,P<0.001)。而二者生存率比较:40.00%(10/25)vs65.12%(28/43),差异有统计学意义(χ2=4.05,P<0.05)。MBP未突变组IL-10水平明显低于健康对照组[(67.86±10.58)ng/L](t=5.42,P<0.001)。结论重型乙肝患者MBP基因仅存在密码子54突变。MBP基因突变使IL-10水平明显降低,免疫抑制和抗炎作用减弱,导致肝炎重症化,生存率降低。

Objective To study the influence of mutations in mannose binding protein（MBP） gene on the interleukin-10（IL-10） production and the prognosis of patients with severe hepatitis B.Methods A total of 68 patients with severe hepatitis B were randomly selected for the study.The exon 1 of MBP gene was amplified by polymerase chain reaction（PCR） and sequenced using Beckman-Coulter CEQ 8000 genetic analyzer.The serum levels of IL-10 were determined by enzyme-linked immunosorbent assay（ELISA） and compared between patients and healthy individuals.The 3-month survival rate of severe hepatitis patients was compared for the groups with and without mutations.Results A mutation in codon 54 of MBP gene was found in patients with severe hepatitis B.The frequency of the gene mutation was 36.76%（25/68）.The serum level of IL-10 was significantly lower in MBP mutations group[（38.92±6.84）pg/ml]than in MBP wild group[（55.75±9.71）pg/ml]（t=8.35,P0.001）.The 3-month survival rate of patients was lower in the group with the gene mutation（40.00%,10/25）than in the group without the mutation（65.12%,28/43）（χ2=4.05,P0.05）.The serum level of IL-10 was markedly lower in patients than in healthy controls[（67.86±10.58）pg/ml]（t=5.42,P0.001）.Conclusions The codon 54 mutation of MBP gene was the only mutant found in patients with severe hepatitis B.The MBP gene mutation may reduce IL-10 production and affect the survival of severe hepatitis B patients.