What is the clinical evidence from this study?

Study design: Observational. Population: Ischemic stroke (n=1003). Intervention: rs5065 G allele carrier status (AG+GG) vs. rs5065 AA genotype. Primary outcome: Embolic stroke of undetermined source (ESUS) vs other defined stroke etiologies (OR 1.35, 95% CI 1.01-1.80, p=0.044).

What question did this study set out to answer?

This study aims to evaluate the relationship between the genetic variant rs5065 and biomarkers in ischemic stroke etiology.

May 8, 2026

Abstract Number: Esoc2026a1967 Genetic Predictors of Atrial Natriuretic Peptides and Circulating Biomarkers in the Context of Etiological Diagnosis of Ischemic Stroke

Key Result

The rs5065 G allele was more frequent in patients with embolic stroke of undetermined source than other stroke etiologies (69.1% vs 62.4%; OR 1.35; 95% CI 1.01-1.80; p=0.044).

Key Points

This study aims to evaluate the relationship between the genetic variant rs5065 and biomarkers in ischemic stroke etiology.
Enrolled 1,003 patients with ischemic stroke at Hannover Medical School between December 2020 and July 2023.
Performed genotyping using Axiom myDesign Genotyping-Array and measured MR-proANP levels via fluorescence immunoassay.
Conducted descriptive analyses to explore the association between rs5065, MR-proANP levels, and ESUS.
G allele carriers (rs5065) were more frequent in ESUS than in other stroke etiologies (69.1% vs 62.4%, p-chi2: 0.044, OR 1.35, 95%CI: 1.01-1.80).
After adjusting for Essen Stroke Risk-Score, higher odds of ESUS remained for G allele carriers (aOR: 1.37, 95%CI: 1.02-1.84).
No significant differences in MR-proANP levels across genotypes were noted (p Mann-Whitney-U: 0.8).

Study Design

Type

Observational (n=1,003)

Multicenter

Structured PICO

Does the rs5065 genetic variant of the NPPA gene associate with MR-proANP levels and ESUS in patients with ischemic stroke?

Population

1,003 patients with ischemic stroke (288 classified as ESUS, 715 as another defined etiology) enrolled at Hannover Medical School.

Intervention

Presence of the dominant G allele (AG+GG) of the rs5065 genetic variant of the NPPA gene

Comparator

AA genotype of the rs5065 genetic variant

Outcome

Association with ESUS and MR-proANP serum concentrationsurrogate

The rs5065 G allele is enriched in patients with ESUS compared to other ischemic stroke etiologies, independent of MR-proANP levels, suggesting a potential genetic link to cardioembolic stroke risk.

Main Result

Effect estimate: OR 1.35 (95% CI 1.01-1.80)

Absolute Event Rate: 69.1% vs 62.4%

p-value: p=0.044

Abstract

Abstract Background and aims Mid-regional pro-atrial natriuretic peptide (MR-proANP) serves as a biomarker for cardioembolic stroke (CES). rs5065, a genetic variant of the Natriuretic Peptide A (NPPA)-gene encoding ANP, remains insufficiently studied in stroke etiologies. Within the PHEGAESUS-study, a phenotype-genotype association study investigating ESUS, we conducted a targeted biomarker analysis to evaluate the impact of rs5065 on MR-proANP and stroke etiology. Methods Between December 2020 and July 2023, patients with ischemic stroke were enrolled at Hannover Medical School. Genotyping was performed using Axiom myDesign Genotyping-Array. MR-proANP serum concentration was measured via fluorescence immunoassay, if samples were available more than 24 hours after stroke onset. Descriptive analyses were performed to elucidate an association between rs5065, MR-proANP-level and ESUS. Results After quality control, 1,003 patients with clinical and SNP-data were available (288 classified as ESUS, 715 as another defined etiology). In the dominant model (AG+GG vs AA), G allele carriers were more frequent in ESUS than in other stroke etiologies (69.1% vs 62.4%, p-chi2: 0.044, OR 1.35, 95%CI: 1.01-1.80). After adjustment for Essen Stroke Risk-Score, the association of rs5065 carrier status with higher odds of ESUS (aOR: 1.37, 95%CI: 1.02-1.84) remained. No differences of MR-proANP-level across the genotypes were observed (median (interquartile range): AG+GG n=92: 99.1 (83.8)pmol/l vs AA n=52: 91.5 (118.8) pmol/l, p Mann-Whitney-U: 0.8). Conclusions The dominant G allel of rs5065 does not seem to influence MR-proANP-level, but is enriched in ESUS patients. Investigation of NPPA-genomic region may improve better understanding of genetic variances, biomarkers and ESUS. Conflict of interest Rebecca Menkhaus: nothing to disclose, Gerrit M Grosse: nothing to disclose, Johannes Teller: nothing to disclose, Rieke Ringslstetter: nothing to disclose, Maria M Gabriel: nothing to disclose, Vinicius D Gastaldi: nothing to disclose, Hannelore Ehrenreich: nothing to disclose, Karin Weissenborn: nothing to disclose, Anika Grosshennig: nothing to disclose, Johanna Ernst: nothing to disclose

Bookmark