The Effect of Renalase rs2576178 and rs10887800 Polymorphisms on Ischemic Stroke Susceptibility in Young Patients (<50 Years): A Case-Control Study and In Silico Analysis

Abstract

Background. Ischemic stroke (IS) is the most common form of cerebrovascular accident which its precise etiology remains mysterious. Renalase is a catecholamine-degrading enzyme playing a major role in blood pressure control. Recent studies show the effect of renalase activity on various diseases like IS. In the current study, we examined the possible effects of renalase gene (RNLS) rs2576178 and rs10887800 variants at the 5 ${}^{\prime }$ -flanking and intron 6 regions on IS, respectively. Methods. One hundred and fifty-four IS patients younger than 50 years and 165 age- and sex-matched controls were recruited in the study. For genotyping of rs2576178 and rs10887800 variants, the PCR-RFLP method was used. Results. The RNLS rs10887800 AG genotype was more repeated in IS patients, but the difference was marginally nonsignificant ( $P=0.054$ ). This variant was associated with IS in the overdominant model, and the AG genotype is associated with a1.6-fold increased risk of IS compared to AA+ GG genotypes ( $\text{OR}=1.6$ , 95% CI: 1-2.5, $P=0.033$ ). No relationship was observed between RNLS rs2576178 polymorphism and IS in all genetic models. The findings of the haplotype and combination effects of rs10887800 and rs2576178 variants on IS showed no significant association. The in silico analysis showed no effect of rs2576178 and rs10887800 polymorphisms in the RNA structure, but the alteration of RNA sequence in rs2576178 results in the lack of a MBNL1 protein binding site. Conclusions. RNLS rs10887800 but not rs2576178 polymorphism was associated with IS susceptibility in the overdominant model (AG vs AA+ GG genotypes).