An explorative epigenome-wide association study of plasma renin and aldosterone concentration in a Ghanaian population: the RODAM study.

BACKGROUND: The epigenetic regulation of the renin-angiotensin-aldosterone system (RAAS) potentially plays a role in the pathophysiology underlying the high burden of hypertension in sub-Saharan Africans (SSA). Here we report the first epigenome-wide association study (EWAS) of plasma renin and aldosterone concentrations and the aldosterone-to-renin ratio (ARR). METHODS: Epigenome-wide DNA methylation was measured using the Illumina 450K array on whole blood samples of 68 Ghanaians. Differentially methylated positions (DMPs) were assessed for plasma renin concentration, aldosterone, and ARR using linear regression models adjusted for age, sex, body mass index, diabetes mellitus, hypertension, and technical covariates. Additionally, we extracted methylation loci previously associated with hypertension, kidney function, or that were annotated to RAAS-related genes and associated these with renin and aldosterone concentration. RESULTS: We identified one DMP for renin, ten DMPs for aldosterone, and one DMP associated with ARR. Top DMPs were annotated to the PTPRN2, SKIL, and KCNT1 genes, which have been reported in relation to cardiometabolic risk factors, atherosclerosis, and sodium-potassium handling. Moreover, EWAS loci previously associated with hypertension, kidney function, or RAAS-related genes were also associated with renin, aldosterone, and ARR. CONCLUSION: In this first EWAS on RAAS hormones, we identified DMPs associated with renin, aldosterone, and ARR in a SSA population. These findings are a first step in understanding the role of DNA methylation in regulation of the RAAS in general and in a SSA population specifically. Replication and translational studies are needed to establish the role of these DMPs in the hypertension burden in SSA populations.

The Role of the Microbiome in Cancer and Therapy Efficacy: Focus on Lung Cancer.

The microbiome is extremely important for human health; more recently its role in the context of cancer became clear. Microbial effects range from enhancing cancer immunity and cancer therapy efficacy, to promoting cancer progression and inhibiting treatment efficacy. These broad implications led researchers to investigate these specific interactions, as well as how modification of the microbiome can improve cancer survival and treatment efficacy. While these interactions are better established for cancers such as gastric cancer, they are far less understood in others. As non-small cell lung cancer (NSCLC) makes up the majority of lung cancer cases, and is among the top causes of cancer deaths worldwide, understanding the mechanisms by which the microbiome may impact progression and treatment is crucial to improve patient survival and treatment response. A literature review was conducted to reveal the crosslink between human microbiome and lung cancer. This includes immune priming, induction of pro- or anti-tumor response, and the local effects of intra-tumoral microbiota. Overall, this is a complex multifactorial relationship, and there are broad implications as to how this knowledge can improve cancer treatment. Solutions include manipulation of the microbiome using probiotics, bacterial vaccines and antibiotics. Bacteria biomarkers may also be used as a diagnostic tool.