Mol Biol Rep. 2026 Oct 8;53(1):1684. doi: 10.1007/s11033-026-12880-x.
ABSTRACT
BACKGROUND: Heat-resistant obscure (Hero) proteins are a recently described class of intrinsically disordered proteins with chaperone-like activity. C19orf53 (Hero11) suppresses TDP-43 aggregation and is linked to mTORC1 signaling, suggesting a potential role in cellular pathways relevant to coronary artery disease (CAD). We investigated whether C19orf53 genetic variants are associated with CAD risk.
METHODS AND RESULTS: We genotyped seven C19orf53 single-nucleotide polymorphisms (SNPs) in 2,164 unrelated individuals of Russian ethnicity from Central Russia, including 836 patients with CAD and 1,328 controls. Associations with CAD risk and clinical traits were assessed using regression analyses with permutation correction, followed by functional annotation with bioinformatical resources. SNPs rs11666524 (effect allele [EA] A, OR = 1.21, 95% CI 1.02-1.45, p = 0.04) and rs2277947 (EA A, OR = 1.22, 95% CI 1.01-1.46, p = 0.03) were associated with increased CAD risk in the entire cohort. The strongest effects of C19orf53 SNPs were observed in subgroups without major CAD risk factors for: non-smokers (p = 0.02 for rs10104, rs11666524, and rs2277947); patients with normal fresh fruit/vegetable intake (p = 0.02 for rs10104, and rs346158; p = 0.016 for rs11666524, p = 0.007 for rs2277947, p = 0.04 for rs8107914); and in patients without obesity (p = 0.02 for rs10104, p = 0.01 for rs11666524, p = 0.004 for rs346157, p = 0.01 for rs2277947). Moreover, C19orf53 SNPs contribute to alterations in coagulation parameters.
CONCLUSIONS: C19orf53 variants are associated with CAD susceptibility and coagulation-related traits, with effects modified by major lifestyle and metabolic risk factors.
PMID:42848261 | DOI:10.1007/s11033-026-12880-x