A recent research study has pinpointed novel genetic and molecular factors that could unveil fresh avenues for treating patients post their initial stroke. The study revealed CCL27 and TNFRSF14, two proteins linked to subsequent MACE (Major Adverse Cardiovascular Events) following a stroke but not the primary stroke itself. These proteins are recognized for triggering inflammation, a significant contributor to stroke development and various chronic ailments.
By detecting genetic indicators in inflammation, the study highlighted potential correlations with second stroke occurrences or other major cardiovascular incidents post an individual’s initial stroke, which could potentially aid in pinpointing drug targets to mitigate stroke-induced disabilities and fatalities.
Individuals who undergo an arterial ischemic stroke (AIS) or transient ischemic stroke (TIA) face an elevated risk of encountering subsequent strokes or other significant adverse cardiovascular incidents (MACE). This underscores the crucial necessity to identify risk factors and therapies to prevent such recurring events.
A collaborative study led by the Boston University School of Public Health (BUSPH), the National Institute for Health and Care Research (NIHR) Bristol Biomedical Research Centre (Bristol BRC), and Veteran’s Affairs Boston Healthcare System (VA Boston), illuminated potential genetic and molecular risk elements that may reveal innovative treatment pathways post an individual’s primary stroke.
Featured in Stroke, a publication of the American Heart Association, the research identified CCL27 and TNFRSF14 as proteins associated with subsequent MACE but not initial strokes. These proteins are known to initiate inflammation, which significantly contributes to stroke evolution and various chronic diseases.
“Prior studies have hinted at the link between inflammation and incident AIS/MACE, yet our study uncovered the potential involvement of these causal proteins in subsequent MACE, potentially paving the way for novel drug targets,” quoted Nimish Adhikari, co-lead author of the study and a biostatistics PhD student at BUSPH and VA Boston. The study was co-led by Andrew Elmore, senior research associate in health data science at NIHR Bristol BRC.
Employing genetic details and medical history from the VA’s Million Veteran Program and UK Biobank, the research team conducted ancestry-specific genome-wide association studies (GWAS) to identify links between DNA and initial as well as subsequent AIS and MACE.
The study encompassed 93,422 individuals who encountered an initial stroke, with 51,929 facing subsequent MACE and 45,120 experiencing subsequent AIS.
Through population-specific analyses, two notable genetic variations were observed: rs76472767 in the African ancestry GWAS, near the RNF220 gene on chromosome 1 for subsequent MACE, and rs13294166 near the LINC01492 gene on chromosome 9 in the same ancestry GWAS for subsequent AIS.
“We delved into the data to explore if certain molecules were correlated with either initial or subsequent conditions,” elucidated Elmore. “This exploration led us to identify a connection between specific molecules involved in inflammation and the outcomes of stroke and MACE.”
Although the incidence of stroke has diminished globally over the past three decades, it still stands as the second leading cause of mortality and third in disability worldwide, posing a significant public health challenge. Stroke disproportionately impacts populations across racial, ethnic, socioeconomic, and geographical boundaries, exacerbating health disparities in both affluent and underprivileged nations. Discovering fresh drug targets for innovative therapeutic interventions that impede stroke progression could potentially rescue millions from stroke-induced disabilities and fatalities.
It remains unknown whether targeting other modifiable stroke risk factors could offer efficacious treatment paths post an initial stroke occurrence.
“We are eager to expand this research into other cardio-metabolic outcomes beyond stroke,” shared Gina Peloso, co-senior and corresponding author, and associate professor of biostatistics at BUSPH.
Co-senior authors, Lavinia Paternoster, associate professor in genetic epidemiology at NIHR Bristol BRC and Bristol Medical School, and Kelly Cho, director of data science and analytics at the division of population health and data science, VA Boston Healthcare System, and associate professor of medicine at Mass General Brigham, Harvard Medical School, also contributed to the study.
