The relationship between sex hormone-binding protein and non-alcoholic fatty liver disease using Mendelian randomisation.

BACKGROUND: The incidence of non-alcohol fatty liver disease (NAFLD) has been increasing annually with the improvement of living standards. Numerous epidemiological observations have linked sex hormone-binding protein (SHBG) levels to NAFLD. However, evidence of the causal role of SHBG in the development and progression of NAFLD is still absent. Therefore, a systematic assessment of the causal relationship is needed. METHOD: A two-sample Mendelian randomisation (MR) analysis was conducted. Genome-wide association study (GWAS) data for SHBG were obtained online from the IEU database (ebi-a-GCST90012111) as exposure. GWAS data from the NAFLD of the Finngen consortium were used for preliminary analysis, while NAFLD data from another GWAS involving 8434 participants were used for replication and meta-analyses. Causal effects were investigated with inverse variance weighted (IVW), weighted median and MR-Egger regression. Sensitivity analyses including Cochran's Q test, leave-one-out analysis and MR-Egger intercept analysis were simultaneously conducted to assess heterogeneity and pleiotropy. RESULTS: After rigorous selection, 179 single-nucleotide polymorphisms (SNPs) were identified as strongly correlated instrumental variables. Preliminary analysis suggested a significant causal relationship between genetically determined serum SHBG levels and NAFLD [odds ratio (OR) IVW = .54, 95% confidence interval (CI) = .30-.98, p = .043], supported by the results of the replication analysis (ORIVW = .61, 95% CI = .46-.81, p = .0006) and further meta-analysis (OR = .59, 95% CI = .46-.77, p < .0001). CONCLUSION: The genetic tendency to high levels of SHBG was causally correlated with a reduced risk of NAFLD, indicating that circulating high levels of SHBG was a protective factor for NAFLD.

[GK-2 prosthetic heart valve: a 20-year clinical experience].

OBJECTIVE: The aim of this study is to analyze our 20-year clinical results with 413 GK-2 mechanical heart valves. METHODS: 123 men and 204 women with a mean age of 38.62 +/- 10.14 years accepted cardiac valve replacements. Ninety-one percent had NYHA class III or IV heart function. The mitral position was in 205 patients, aortic position in 31 patients, aortic and mitral in 86 patients, and tricuspid position in 5. Altogether 296 mitral prosthetic valves and 117 aortic prosthetic valves were implanted. Follow-up is 91% and extended 0.5 to 19.6 years with cumulative 2440.7 patient-years. RESULTS: The early mortality was 3.36% (11/327). There were 24 late deaths (0.98% per patient-year). The actuarial probability of survival was 93.31% +/- 0.03% at 5 years, 89.59 +/- 2.1% at 10 years, 83.61% +/- 6.09% at 15 years. The linearized rate of thromboembolism was 0.29% pt-yr, the rate of bleeding event 0.49% pt-yr. In 91.98% of survivors NYHA functional performance have improved to class II or I. CONCLUSION: Early and long-term results in our hospital demonstrate that the GK-2 prosthetic heart valve exhibits excellent hemodynamic properties, mechanical durability and a low incidence of valve-related complications.