RORA polymorphisms are associated with ischemic stroke

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.