RORA polymorphisms are associated with ischemic stroke

IF 1 Q4 GENETICS & HEREDITY

Gene Reports Pub Date : 2025-03-05 DOI:10.1016/j.genrep.2025.102191

Mohammad Samadian , Fatemeh Sadat Feghahati , Maryam Sheikhvand , Arash Safarzadeh , Arezou Sayad , Soudeh Ghafouri-Fard

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引用次数: 0

Abstract

Introduction

RAR Related Orphan Receptor A (RORA) encodes a nuclear hormone receptor that participates in the pathoetiology of several disorders.

Objective

We aimed to evaluate association between two RORA variants (rs11639084 and rs4774388) and risk of ischemic stroke among Iranians.

Methods

These polymorphisms were genotyped using 4P-ARMS-PCR method.

Results

The rs11639084 polymorphism was associated with risk of stroke in all assumed inheritance models. T allele of this polymorphism was identified as the risk allele increasing the risk of ischemic stroke with OR (95 % CI) of 18.64 (13.58–25.57), P < 0.0001 and AIC = 29.4. Notably, the TT genotype was found to increase risk of this condition compared with CC genotype (OR (95 % CI) = 309.6 (142.2–683.2)) and CC + TC genotypes (OR (95 % CI) = 62.37 (30.06–129.4)). Since AIC estimates the quality of each model relative to other models, allelic model seems to be the best model for appraisal of the association between rs11639084 and risk of ischemic stroke. The rs4774388 polymorphism was associated with risk of stroke in all assumed inheritance models, except for over-dominant model. C allele of this polymorphism was reported to be the risk allele increasing the risk of ischemic stroke with OR (95 % CI) of 8.56 (6.4–11.43), P < 0.0001 and AIC = 29.6. Accordingly, the CC genotype increased susceptibility to ischemic stroke compared with TT genotype (OR (95 % CI) = 22.4 (14.6–42.5)), as well as combination of the other two genotypes (OR (95 % CI) = 12.92 (8.18–20.4)). Similar to the other polymorphism, the highest AIC value belonged to the allelic model.

Conclusions

In brief, we showed associations between two RORA polymorphisms and susceptibility to ischemic stroke in Iranian population. RORA might be the functional link between abnormality in circadian rhythm and risk of ischemic stroke. Moreover, this gene might explain the shared genetic background between obesity and stroke.

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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.