In collaboration with Sepiso Masenga, MSc, PhD, senior lecturer and researcher at Mulungushi University School of Medicine and Health Sciences in Zambia, Annet Kirabo, DVM, MSc, PhD, associate professor of Medicine at Vanderbilt University Medical Center, has received a new two-year exploratory research grant to study the link between salt taste sensitivity and salt intake, blood pressure, hypertension and genetic variations in individuals of African descent.
The Fogarty International Center and the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health funded the project. Masenga and Kirabo are co-principal investigators.
Hypertension prevalence is high in sub-Saharan Africa, specifically in persons living with HIV, and it is a risk factor for stroke, heart attack, kidney disease and death. Poor salt taste sensitivity is linked to high salt intake and is likely to increase the risk of developing hypertension, especially among persons with HIV, where the risk is heightened.
“Inclusion of persons with HIV in our studies on salt sensitivity of blood pressure and hypertension offers us a unique opportunity to be able to explore and provide new solid insights on the risk induced by HIV infection and treatment,” Masenga said.
The effects of salt on blood pressure are more pronounced in individuals whose blood pressure reflects changes in dietary salt intake or depletion (SSBP) and those with certain specific genetic variations in the taste receptor genes who cannot taste salt more easily.
Masenga noted salt consumption is generally high in low- and middle-income countries, including Zambia.
“Dietary salt is one of the driving factors that directly contribute to the development of hypertension by promoting pathological changes in the vasculature and indirectly through immune activation and inflammation,” Kirabo added.
To determine if salt taste sensitivity is associated with salt intake and inflammation in persons with HIV, the study team will conduct clinical studies utilizing inflammatory biomarkers, food recall and lab tests for assessment between cohorts of people with and without HIV.
“We have so much experience in studying novel pathways and immune mechanisms of salt-sensitive hypertension and we are confident to discover new additional insights linking genetic variations to salt taste thresholds and salt sensitivity of blood pressure and how HIV status likely modifies the relationships,” Kirabo said.
The sodium channel ENaC mediates salt entry into immune cells, forming reactive molecules called isolevuglandins and an inflammatory, autoimmune-like state in hypertension. The study will determine if genetic variations in ENaC are associated with salt taste perception, SSBP, and hypertension in HIV. The study will include genetic sequencing of taste receptor genes to evaluate the linkage between salt taste sensitivity and SSBP in persons with and without HIV.
“Prior studies from western countries indicate that there is a genetic predisposition to salt taste sensitivity suggesting that preference for salty taste may be a driver of salt intake. However, to date, there is scarcity of data on taste genetic risk scores and salt taste sensitivity in African populations including Zambia,” Masenga said.
“Furthermore, genetic association studies in this area are limited to people of European descent, with more research needed in populations of different ethnic backgrounds, such as African populations. Our project addresses multiple critical gaps in the literature including the lack of understanding of genetic predispositions to salt taste sensitivity in African populations and how this relates to salt-sensitive hypertension in persons with and without HIV.”
He added, “I have been working with Dr Kirabo since 2017, and joined her lab during my PhD studies at Vanderbilt. I was amazed at how much compelling and innovative science around hypertension she was leading. She is a prolific scientist and leader in this field, and I am profoundly excited that her expertise and immense experience will touch the lives of Zambia in a way that is unique through this new grant. Her mentorship goes beyond international borders and through herself and others at the Vanderbilt Institute for Global Health including Dr. Douglas Heimburger and Holly Cassell, we at Mulungushi University are confident to benefit immensely from this research experience.”
Part of the preliminary data for this study originated from Masenga’s doctoral dissertation research, his research project as a Fogarty Global Health Fellow, and as a Vanderbilt Institute for Research Development and Ethics (VIRDE) scholar.
In 2020, Masenga received his PhD in immuno-pathology from the University of Zambia (UNZA), with support from the UNZA-Vanderbilt Training Partnership for HIV-Nutrition-Metabolic Research program. He completed his Global Health fellowship in 2021 with support from the Fogarty International Center of the National Institutes for Health. In 2022, he completed an in-person one-month grant development training course at Vanderbilt. As a (VIRDE) scholar, he engaged with Kirabo and other VUMC faculty and staff in preparing this successful grant proposal.
The UNZA-Vanderbilt partnership is a “sandwich” PhD program. The University of Zambia awards the degree with courses taken at Vanderbilt and includes co-mentorship from Vanderbilt and UNZA investigators. Masenga leads the HAND Research Group at Mulungushi University, focusing on HIV, hypertension, nutrition, diabetes, and dyslipidemia in sub-Saharan Africa.
Working collaboratively, Masenga and faculty from VUMC and UNZA have coauthored several manuscripts, secured funding for this exploratory grant, and developed foundational research for future grant opportunities, including plans for a biobank of saliva and blood samples of persons from Africa for future genomic, proteomic and metabolomic analyses.