• PINK1 and PINK1-AS1 in Multiple Sclerosis
  • mona patoughi ,1,*
    1. Department of Biology, Science and Research Branch, Islamic Azad university, Tehran, Iran


  • Introduction: Recent investigations which have aimed at unraveling the etiology of multiple sclerosis (MS), have underscored the role of mitochondria in this disorder. PTEN-induced kinase 1 (PINK1) gene encodes a serine/threonine kinase that protects mitochondria and maintains its normal function. In the current project, we compared expression level of PINK1 and a long non-coding RNA which is transcribed antisense to this gene (PINK1-AS) in peripheral blood of MS patients and normal persons.
  • Methods: The study was conducted on 100 persons including 50 RRMS patients and the same number of age- and sex-matched controls. Peripheral blood specimens were used for RNA extraction. The process was done according to the instructions provided in Hybrid-RTM blood RNA extraction Kit (GeneAll Biotechnology, South Korea). Next, RNA was converted to cDNA using FIREScript RT cDNA Synthesis Kit (Solis BioDyne, Estonia). Expressions of PINK1 and PINK1-AS genes were quantified in peripheral blood of enrolled persons using RealQ Plus Master Mix Green (AMPLICON, Denmark). All reactions were executed in the rotor gene 6000 machine (Corbett, Australia) in duplicate.
  • Results: Peripheral expression of PINK1-AS was significantly higher in MS patients compared with healthy individuals. Such significant difference in PINK1-AS expression was also detected in male patients compared with male controls. However, the difference was not significant between female subgroups. Expression of PINK1 was not different between cases and controls. Univariate analysis showed significant difference in age, disease duration, progression index and age at disease onset between males and females (P values of 0.041, 0.001, <0.0001 and 0.007 respectively). There was a trend toward correlation between expression levesl of PINK1 and PINK1-AS (r=0.26, P=0.074). However, expressions of either genes were correlated with any of the demographic or clinical data. The current study propose PINK1-AS as a puttaive culpript in the pathogenesis of MS and recommend conduction of additional studies to unravel the mechanism.
  • Conclusion: we could not detect any significant difference in the expression of PINK1 in the peripheral blood of cases and controls. Expression of PINK1-AS was significantly higher in MS patients compared with healthy individuals. But such significant difference was detected only between male patients and with male controls. This observation might be due to the presence of a gender-based regulatory mechanism for PINK1-AS expression or difference in the pathogenic process of disease in male and female MS patients. Based on the lack of sufficient data regarding the effects of sex hormones on expression of PINK1-AS, we could not definitely deduce the underlying mechanism of this observation. However, further analysis of association between demographic factors and gender has shown significant difference in age, disease duration, progression index and age at disease onset between males and females which in accordance with the second hypothesis. In our limited cohort of patients, disease duration values were greater in females compared with males. However, progression index was significantly higher in males compared with females. These gender-based differences in MS course have also been documented in large cohorts of patients where Ribbons et al. reported more rapidly accumulation of disability in male patients with relapse-onset MS compared with female patients
  • Keywords: multiple sclerosis, PINK1, PINK1-AS