肿瘤坏死因子-α-238基因多态性及血清学水平与乙型肝炎病毒慢性感染结果的关系

目的 探讨肿瘤坏死因子（TNF-α）基因多态性与乙型肝炎病毒慢性感染结果之间的关系以及乙型肝炎病毒慢性感染患者血清中TNF-α水平在慢性乙肝发展中的临床意义。方法 运用聚合酶链反应-限制性片段长度多态性分析的方法检测TNF-α基因启动子区-238位点单个核苷酸多态性在不同临床类型的慢性HBV感染者及健康对照者中的分布频率;应用ELISA方法检测血清TNF-α浓度水平。结果 TNF-α-238位点G/A和G/G基因型频率以及A等位基因频率分布在实验组和健康对照组的差异无统计学意义。慢性乙型肝炎组、肝硬化组、乙型肝炎肝衰竭组和健康对照组比较,血清TNF-α均有不同程度升高,TNF-α（ng/L）取对数值后经方差分析,差异有统计学意义（P〈0.01）;组间两两比较,差异均有统计学意义（P〈0.01）,血清TNF-α水平乙型肝炎肝衰竭组〉肝硬化组〉慢性乙型肝炎组〉健康对照组。结论 TNF-α-238位点基因型与乙型肝炎易感性无明显相关性。TNF-α与乙型肝炎类型、肝损伤程度有密切关系。     

Clinical outcome and virological characteristics of hepatitis B-related acute liver failure in the United States

The role of hepatitis B virus (HBV) genotypes in the outcome of acute HBV infection is unclear. In this study, we aimed to evaluate the clinical and virological features of patients with hepatitis B-related acute liver failure (HBV-ALF) in the US. Clinical and laboratory features of consecutive patients with HBV-ALF from the US ALF Study Group were analysed. Prevalence of HBV genotypes, precore stop (G1896A) and core promoter dual (T1762A, A1764T) variants among patients with HBV-ALF were compared with a cohort of 530 patients with chronic HBV infection. Thirty-four HBV-ALF patients were studied: mean age 41 years, 56% men, 25 had detectable HBV-DNA. HBV genotypes A, B, C and D were found in 36, 24, 8 and 32% patients, respectively. Precore stop and core promoter dual variants were detected in 32 and 44% of patients, respectively. Twenty-three (68%) patients survived: 14 after liver transplant, nine without transplant. Older age was the only independent factor associated with poor outcome. Compared with patients with chronic HBV infection, patients with ALF were more likely to be non-Asians (88% vs 44%, P = 0.005) and to have genotype D (32% vs 10%, P < 0.01). A higher prevalence of HBV genotype D persisted even after matching for race and HBeAg status (32% vs 16%, P = 0.007). We concluded that HBV genotype D was more frequently found in patients with HBV-ALF than those with chronic HBV infection in the US. Further studies are needed to determine if HBV genotypes play a role in the outcome of acute HBV infection.     

Influence of apolipoprotein A-1 promoter polymorphism on lipid levels and responses to dietary change in Finnish adults

Objectives. To analyse the association between the G/A polymorphism in the apolipoprotein A-1 (apo A-1) promoter region and plasma lipid levels, as well as their responses to dietary change, in Finnish adults.
Subjects and design. Blood samples from 86 subjects (42 men, 44 women) who attended a dietary intervention study carried out in North Karelia in 1993 were available for the current analysis. The diet study consisted of a 2-week baseline period, followed by an 8-week intervention period, and an 8-week switchback period.
Intervention. Diet was modified to a low-fat, low-cholesterol diet during the dietary intervention.
Main outcome measures. Fasting plasma lipid, lipoprotein and apolipoprotein levels were determined.
Results. At baseline, the high-density lipoprotein (HDL) cholesterol and apo A-1 levels were higher ( P <0.01) and the triglyceride levels were lower ( P <0.05) in men, but not in women, with the A allele. The differences in HDL cholesterol and apo A-1 levels between genotypes remained during the low-fat, low-cholesterol diet and switchback periods. Apart from the difference between responses in apo A-1 during switchback to the original diet, lipid responses to dietary change did not differ significantly between genotypes.
Conclusion. Our findings indicate a significant association between the apo A-1 promoter polymorphism and plasma apo A-1 and HDL-cholesterol in men. In theory, the higher plasma HDL-cholesterol and apo A-1 levels in the GA/AA group may confer some protection against coronary artery disease. The differences in HDL-cholesterol and apo A-1 levels between genotypes persisted during different diets suggesting that the possible benefit is independent of fat and cholesterol intake.