The fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P=9.65310 25) and diastolic BP (P=7.61310 23) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9.0310 23). Next-generation RNA sequencing revealed that upregulated renal expression of FGF1 or of each of the three FGF1 mRNA isoforms individually was associated with higher BP. FGF1-stratified coexpression analysis in two separate collections of human kidneys identified 126 FGF1 partner mRNAs, of which 71 and 63 showed at least nominal association with systolic and diastolic BP, respectively. Of those mRNAs, seven mRNAs in five genes (MME, PTPRO, REN, SLC12A3, and WNK1) had strong prior annotation to BP or hypertension. MME, which encodes an enzyme that degrades circulating natriuretic peptides, showed the strongest differential coexpression with FGF1 between hypertensive and normotensive kidneys. Furthermore, higher level of renal FGF1 expression was associated with lower circulating levels of atrial and brain natriuretic peptides. These findings indicate that FGF1 expression in the kidney is at least under partial genetic control and that renal expression of several FGF1 partner genes involved in the natriuretic peptide catabolism pathway, reninangiotensin cascade, and sodium handling network may explain the association between FGF1 and BP. Essential hypertension is a net product of genetic factors and environmental exposure acting together on regulatory systems in key organs for BP homeostasis. The kidney is central to BP regulation and drives the development of hypertension through numerous mechanisms including glomerular hemodynamics, tubular reabsorption of sodium, actions of the renin-angiotensin system, and natriuretic peptides. 1 Rare genetic variants that affect expression of molecules and pathways operating within the kidney lead to elevated BP in monogenic forms of hypertension. 2 Several common variants in genes associated with BP and/or susceptibility to hypertension are also believed to act through the

There is an increasing appreciation for the role of the human Y chromosome in phenotypic differences between the sexes in health and disease. Previous studies have shown that genetic variation within the Y chromosome is associated with cholesterol levels, which is an established risk factor for atherosclerosis, the underlying cause of coronary artery disease (CAD), a major cause of morbidity and mortality worldwide. However, the exact mechanism and potential genes implicated are still unidentified. To date, Y chromosome-linked long non-coding RNAs (lncRNAs) are poorly characterized and the potential link between these new regulatory RNA molecules and hepatic function in men has not been investigated. Advanced technologies of lncRNA subcellular localization and silencing were used to identify a novel intergenic Y-linked lncRNA, named lnc-KDM5D-4, and investigate its role in fatty liver-associated atherosclerosis. We found that lnc-KDM5D-4 is retained within the nucleus in hepatocytes. Its knockdown leads to changes in genes leading to increased lipid droplets formation in hepatocytes resulting in a downstream effect contributing to the chronic inflammatory process that underpin CAD. Our findings provide the first evidence for the implication of lnc-KDM5D-4 in key processes related to fatty liver and cellular inflammation associated with atherosclerosis and CAD in men.

Coronary artery disease (CAD) is one of the leading causes of morbidity and mortality globally. In the last few years our understanding of the genetic and molecular mechanisms that promote CAD in individuals has increased with the advent of the genome era. This complex inflammatory disease has well-defined environmental risk factors. However, in the last 10 years, studies including genome-wide association studies (GWAS) have clearly demonstrated a genetic influence on CAD. Recently, studies on the human Y chromosome have also demonstrated that genetic variation within the male-specific region of the Y chromosome (MSY) could play a part in determining cardiovascular risk in men, confirming the notion that the increased risk for CAD in men cannot be fully explained through common CAD risk factors. Here, we review the literature about the pathophysiology of CAD, its potential causes and environmental risk factors known so far. Furthermore, we review the genetics of CAD, especially the latest discoveries regarding the implication of the Y chromosome, the most underexplored portion of the human genome to date, highlighting methods and difficulties arising in this research field, and discussing the importance of considering the Y chromosome in CAD research.

Introduction: Hepatocellular carcinoma (HCC) is the leading cause of primary liver cancer with its prevalence continuing to rise. Although the number of cases continues to rise in both developing and developed countries, prognosis remains poor due to a lack of successful treatments. Inspired by the prospect of developing complementary medicines for this condition, we explore several native Australian plants for anti-carcinogenic activity, especially against HCC. Methods: Cytotoxicity assays against HCC cell lines were conducted using various plant extracts. Biochemical profiling of the plant species was conducted for total phenolics and antioxidant capacity, while reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the active apoptotic pathways. Results: Westringia fruticosa and Prostanthera ovalifolia (small-leaved variety) had high antioxidant (410 and 227 mg/g, respectively) and phenolic contents (72.7 and 42.7 mg/g, respectively). P. ovalifolia (small-leaved variety) demonstrated the greatest cytotoxic activity against HepG2 cells (IC 50 4.61 ± 0.98 µg/mL) followed by Solanum laciniatum leaves (11.79 ± 0.43 µg/mL) and fruit extracts (ripe, unripe) (14.85 ± 1.80 and 19 ± 1.32 µg/mL, respectively).RT-PCR results confirmed apoptotic events in HepG2 cells, exposed to ripe and unripe S. laciniatum fruit extracts, via caspase-3 pathway. The highest apoptotic induction occurred after 8 hr. Compared to unripe fruits, ripe fruits induced a greater level of apoptosis, as evidenced by a 73 % higher level of caspase-3 mRNA expression and 22 % lower IC 50 value. Conclusion: With further investigation, these fruits may provide a valuable source of anticarcinogenic compounds for use as chemotherapeutic or complementary therapies.