RESUMO
BACKGROUND: It is known in some studies that higher the LDL-C, the greater the risk of developing cardiovascular disease. However, studies of the causal effects between LDL-C and hypertension are limited by their observational study design, and genetic epidemiology studies of associations between LDL-C and hypertension are lacking, as are studies using data for Koreans. In this study, we confirmed the causal effect of LDL-C on hypertension using Korean chip data. METHOD: The epidemiology and genotype data were collected from the Korean Genome and Epidemiology Study conducted by the Korea National Institute of Health and covered 20,701 subjects. Single-nucleotide polymorphisms associated with LDL-C were selected (p-value < 5 × 10- 8) from the Global Lipids Genetics Consortium database, and Mendelian randomization analysis (MRA) was performed with counted genetic risk scores and weighted genetic risk scores (WGRSs) for 24 single-nucleotide polymorphisms. RESULT: The assumptions for MRA were statistically confirmed, and WGRSs showed a strong association with LDL-C. Interestingly, while the relationship between LDL-C and hypertension was not statistically significant in the observational study, MRA study demonstrated that the risk of hypertension increased as LDL-C increased in both men and women. CONCLUSIONS: The results of this study confirmed that the relationship between LDL-C and hypertension is greatly influenced by genetic information.
RESUMO
OBJECTIVES: Radon, a natural radiation, is the leading environmental cause of lung cancer in never-smokers. However, the radon exposure impact on the mutational landscape and tumor mutation burden (TMB) of lung cancer in never-smokers has not been explored. The aim of this study was to investigate the mutational landscape of lung adenocarcinoma in never-smokers who were exposed to various degrees of residential radon. MATERIALS AND METHODS: To investigate the effect of indoor radon exposure, we estimated the cumulative exposure to indoor radon in each house of patients with lung cancer with a never-smoking history. Patients with at least 2 year-duration of residence before the diagnosis of lung adenocarcinoma were included. Patients were subgrouped based on the median radon exposure level (48 Bq/m3): radon-high vs. radon-low and targeted sequencing of tumor and matched blood were performed in all patients. RESULTS: Among 41 patients with lung adenocarcinoma, the TMB was significantly higher in the radon-high group than it was in the radon-low group (mean 4.94 vs. 2.6 mutations/Mb, P = 0.01). The recurrence rates between radon-high and radon-low group did not differ significantly. Mutational signatures of radon-high tumors showed features associated with inactivity of the base excision repair and DNA replication machineries. The analysis of tumor evolutionary trajectories also suggested a series of mutagenesis induced by radon exposure. In addition, radon-high tumors revealed a significant protein-protein interaction of genes involved in DNA damage and repair (P < 0.001). CONCLUSIONS: Indoor radon exposure increased the TMB in never-smoker patients with lung adenocarcinoma and their mutational signature was associated with defective DNA mismatch repair.
