Obesity and Environmental Risk Factors Significantly Modify the Association between Ischemic Stroke and the Hero Chaperone C19orf53.

The unique chaperone-like properties of C19orf53, discovered in 2020 as a "hero" protein, make it an intriguing subject for research in relation to ischemic stroke (IS). Our pilot study aimed to investigate whether C19orf53 SNPs are associated with IS. DNA samples from 2138 Russian subjects (947 IS and 1308 controls) were genotyped for 7 C19orf53 SNPs using probe-based PCR. Dominant (D), recessive (R), and log-additive (A) regression models in relation to the effect alleles (EA) were used to interpret associations. An increased risk of IS was associated with rs10104 (EA G; Pbonf(R) = 0.0009; Pbonf(A) = 0.0004), rs11666524 (EA A; Pbonf(R) = 0.003; Pbonf(A) = 0.02), rs346158 (EA C; Pbonf(R) = 0.006; Pbonf(A) = 0.045), and rs2277947 (EA A; Pbonf(R) = 0.002; Pbonf(A) = 0.01) in patients with obesity; with rs11666524 (EA A; Pbonf(R) = 0.02), rs346157 (EA G; Pbonf(R) = 0.036), rs346158 (EA C; Pbonf(R) = 0.005), and rs2277947 (EA A; Pbonf(R) = 0.02) in patients with low fruit and vegetable intake; and with rs10104 (EA G; Pbonf(R) = 0.03) and rs11666524 (EA A; Pbonf(R) = 0.048) in patients with low physical activity. In conclusion, our pilot study provides comprehensive genetic and bioinformatic evidence of the involvement of C19orf53 in IS risk.

SERPINE1 mRNA Binding Protein 1 Is Associated with Ischemic Stroke Risk: A Comprehensive Molecular-Genetic and Bioinformatics Analysis of SERBP1 SNPs.

The SERBP1 gene is a well-known regulator of SERPINE1 mRNA stability and progesterone signaling. However, the chaperone-like properties of SERBP1 have recently been discovered. The present pilot study investigated whether SERBP1 SNPs are associated with the risk and clinical manifestations of ischemic stroke (IS). DNA samples from 2060 unrelated Russian subjects (869 IS patients and 1191 healthy controls) were genotyped for 5 common SNPs-rs4655707, rs1058074, rs12561767, rs12566098, and rs6702742 SERBP1-using probe-based PCR. The association of SNP rs12566098 with an increased risk of IS (risk allele C; p = 0.001) was observed regardless of gender or physical activity level and was modified by smoking, fruit and vegetable intake, and body mass index. SNP rs1058074 (risk allele C) was associated with an increased risk of IS exclusively in women (p = 0.02), non-smokers (p = 0.003), patients with low physical activity (p = 0.04), patients with low fruit and vegetable consumption (p = 0.04), and BMI ≥25 (p = 0.007). SNPs rs1058074 (p = 0.04), rs12561767 (p = 0.01), rs12566098 (p = 0.02), rs6702742 (p = 0.036), and rs4655707 (p = 0.04) were associated with shortening of activated partial thromboplastin time. Thus, SERBP1 SNPs represent novel genetic markers of IS. Further studies are required to confirm the relationship between SERBP1 polymorphism and IS risk.