BDNF基因多态性与乙型肝炎肝硬化易感性及病情进展的关联

Relationship between BDNF gene polymorphism and susceptibility to hepatitis B liver cirrhosis and progression of disease

目的探讨脑源性神经营养因子(Brain-derived neurotrophic factor, BDNF)基因多态性与乙型肝炎肝硬化易感性及病情进展的关联。方法选择海南西部中心医院感染科2018年6月-2019年12月收治的乙型肝炎肝硬化患者80例为研究组,同期医院收治的乙型肝炎但未出现肝硬化病理改变的患者80例为对照组。研究组患者按照肝功能分为Grade A组21例、Grade B组29例和Grade C组30例。采用聚合酶链式扩增反应(PCR)对BDNF基因rs6265位点进行扩增;分析不同肝功能分级乙型肝炎肝硬化患者BNDF基因rs6265位点基因型分布及血清BDNF、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和碱性磷酸酶(ALP)水平。结果研究组BDNF基因rs6265位点AA基因型、A等位基因频率高于对照组,GG基因型、G等位基因频率低于对照组,差异均具有统计学意义(P<0.05);校正性别、年龄和乙型肝炎病毒(HBV)-DNA载量常量因素后,携带BDNF基因rs6265位点AA基因型、A等位基因是乙型肝炎肝硬化发生的影响因素(P<0.05);三组不同肝功能分级乙型肝炎肝硬化患者BDNF基因rs6265位点GG、AA基因型频率及ALT、AST、ALP差异具有统计学意义(P<0.05),Grade C组GG、AA型频率及血清ALT、AST、ALP水平高于Grade B组和Grade A组(P<0.05)。结论 BNDF基因rs6265位点AA基因型显著增加本地区居民乙型肝炎肝硬化易感性,且与肝功能分级有关,值得临床筛查。

OBJECTIVE To explore the relationship between the brain-derived neurotrophic factor(BDNF) gene polymorphism and the susceptibility to hepatitis B liver cirrhosis and progression disease. METHODS A tota of;pf 80 patients with hepatitis B liver cirrhosis who were treated in department of infectious diseases of Hainan Western Central Hospital from Jun 2018 to Dec 2019 were assigned as the study group, meanwhile, 80 patients with hepatitis B who did not have pathologic change to liver cirrhosis were set as the control group. The patients of the study group were divided into the grade A group with 21 cases, the grade B group with 29 cases and the grade C group with 30 cases according to the liver function. rs6265 locus of BDNF gene was amplified by polymerase chain reaction(PCR).The genotypes at rs6265 locus of BNDF gene and levels of serum BDNF, alanine aminotransferase(ALT), aspartate aminotransferase(AST) and alkaline phosphatase(ALP) were observed and compared among the hepatitis B liver cirrhosis patients with different grades of liver function. RESULTS The frequencies of genotype AA at rs6265 locus of BDNF gene and allele A were significantly higher in the study group than in the control group, the frequencies of genotype GG and allele G of the study group were significantly lower than those of the control group(P<0.05). After the constant factors gender, age and hepatitis B virus(HBV)-DNA load were revised, the genotype AA at rs6265 locus of BDNF gene and allele A were the influencing factors for the hepatitis B liver cirrhosis(P<0.05). There were significant differences in the frequencies of genotypes GG and AA at rs6265 locus of BDNF gene and levels of ALT, AST and ALP among three groups of hepatitis B liver cirrhosis patients(P<0.05);the frequencies of genotypes GG and AA as well as the levels of serum ALT, AST and ALP of the grade C group were significantly higher than those of the grade B group and the grade A group(P<0.05). CONCLUSION The genotype AA at rs6265 locus of BNDF gene remarkably raise the susceptibility to hepatitis B liver cirrhosis of the local residents, which is associated with the classification of liver function, and it is worthy to conduct clinical screening.