Two Proteins Linked to Increased Stroke Recurrence Risk

Individuals who suffer an arterial ischemic stroke (AIS) or transient ischemic stroke (TIA) face a heightened risk of a subsequent stroke or major adverse cardiovascular event (MACE). Identifying risk factors and effective treatments is crucial to preventing these future occurrences. A recent study has uncovered new genetic and molecular risk factors. These findings may open up new treatment pathways for patients following their initial stroke (1^✔ ✔Trusted Source
Protein Identification for Stroke Progression via Mendelian Randomization in Million Veteran Program and UK Biobank

Go to source). Published in Stroke, a journal of the American Heart Association, the study identified CCL27 and TNFRSF14, two proteins that are associated with subsequent MACE, but not initial strokes. These proteins are known to activate inflammation, which plays a key role in the development of strokes and many chronic conditions and diseases.

“While previous studies have found associations between inflammation and incident AIS/MACE, our study found that these causal proteins may also have a role in subsequent MACE, which could lead to potential novel drug targets,” says study co-lead author Nimish Adhikari, a PhD student in biostatistics at BUSPH and VA Boston. The study was also co-led by Andrew Elmore, senior research associate in health data science at NIHR Bristol BRC.

Ancestry-Specific GWAS Uncovers DNA Associations with AIS and MACE

Utilizing genetic information and medical history data from two large biobanks, the VA’s Million Veteran Program and UK Biobank, the research team conducted ancestry-specific genome-wide association studies (GWAS) to find associations between DNA and incident and subsequent AIS and MACE.

GWAS are typically performed to determine whether individuals have had a medical event for the first time, but applying this method to subsequent MACE events could shed novel insights about stroke progression, information that would be valuable for therapeutic drug identification, the researchers say.

In total, the researchers examined 93,422 individuals who had an incident stroke, among which 51,929 had subsequent MACE and 45,120 had subsequent AIS.

In population specific analyses, they observed two significant genetic variants: rs76472767, near gene RNF220 on chromosome 1 in the African ancestry GWAS for subsequent MACE, and rs13294166, near gene LINC01492 on chromosome 9 in the same ancestry GWAS for subsequent AIS.

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“We used that data to find if there were certain molecules that were associated with either incident or subsequent states,” says Elmore. “From that, we were able to identify a link between certain molecules that play a part in inflammation and these stroke and MACE outcomes.”

While the prevalence of stroke has declined worldwide over the last three decades, it is still the second-leading cause of death and third-leading cause of disability across the globe, and it remains a significant public health issue. Stroke also continues to disproportionately affect populations among racial, ethnic, socioeconomic, and geographical lines, furthering health inequities in both high- and low-income countries. Identifying novel drug targets for new therapeutic interventions that thwart stroke progression could save millions of people from experiencing stroke-related disability and mortality.

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It’s unknown if targeting other modifiable risk factors for stroke could also offer pathways for effective treatment after someone experiences their first stroke.

“We are looking forward to extending this research to other cardiometabolic outcomes beyond stroke,” says co-senior and corresponding author Gina Peloso, associate professor of biostatistics at BUSPH.

Reference:

1. Protein Identification for Stroke Progression via Mendelian Randomization in Million Veteran Program and UK Biobank - (https://www.ahajournals.org/doi/10.1161/STROKEAHA.124.047103)

Source-Eurekalert