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GWAS-linked hot loci predict short-term functional outcome and recurrence of ischemic stroke in Chinese population.


ABSTRACT: In the past decade, an increasing number of genome-wide association studies (GWASs) have been applied to ischemic stroke (IS) susceptibility and recovery. In our study, six GWAS-linked hot loci (ALDH2 rs10744777, HDAC9 rs2107595, ABO rs532436, PATJ rs76221407, LOC105372028 rs1842681 and PTCH1 rs2236406) were selected, genotyped and analyzed in 982 IS patients from northern Chinese population, in order to explore their roles in stroke functional outcome and recurrence risk. We found that PTCH1 rs2236406 was significantly associated with functional outcome after stroke. Further logistic regression analysis revealed the variant genotype TC/CC of rs2236406 as an independent prognostic factor for poor stroke recovery in Chinese population. Meanwhile, we observed that GA/AA genotype of ABO rs532436 was statistically correlated with the increased risk of stroke recurrence, especially for patients with large-artery atherosclerosis. Moreover, multivariate Cox analysis identified ABO rs12342 as an independent predictor for IS recurrence. Further functional annotation analysis demonstrated that rs2236406 and rs2043211 were located in the transcriptionally active region, and could change the regulatory motif, transcription factor binding capacity and expression level of RP11-435O5.5 (antisense to PTCH1) and ABO, respectively. In summary, our results suggested that PTCH1 rs2236406 and ABO rs532436 may be novel genetic markers and potential therapeutic targets for stroke prognosis. More studies are required to confirm our findings and clarify the underlying molecular mechanisms.

PROVIDER: S-EPMC8205681 | BioStudies |

REPOSITORIES: biostudies

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