Circadian rhythm regulating genes in multiple sclerosis: a systematic review and meta-analysis (PP-39)

Introduction:
Multiple sclerosis (MS) as a leading cause of disability among young populations is still under investigation for its pathogenesis. The prevalence of MS increases with latitude, and it is often claimed that the definitive cause of MS is unknown.The circadian rhythm is a crucial process controlled by Circadian Locomotor Output Cycles Kaput (CLOCK) genes that regulate various physiological functions in coordination with environmental cues. Another main regulatory gene of this cycle is Brain and Muscle ARNT-Like Protein 1,also known as Aryl Hydrocarbon Receptor Nuclear Translocator-Like (ARNTL/BMAL-1). CLOCK and ARNTL/BMAL-1 genes regulate the expressions of PER1, PER2,PER3, and cryptochrome by a heterodimeric protein in a positive way, whose expressions are in turn regulated by PER and cryptochrome in a negative feedback loop. This study systematically explores the probable correlation between the ARNTL/BMAL-1, CLOCK, as well as PER1, PER2, and PER3 genes, and MS.
 
Search Strategy:
We conducted a comprehensive literature search in databases including PubMed, Scopus, Embase, and Web of Science for studies published until July 31, 2023 using the terms ((circadian OR ARNTLOR BMAL1 OR CLOCK OR PER1 OR PER2 OR PER3) AND ("Multiple sclerosis")).
Out of 594 results of the database searches, five studies were included. No
significant statistical difference was found between MS patients and the control groups regarding the rs6811520 single nucleotide polymorphisms(SNP) of the CLOCK gene (p;0.05); however, regarding the rs3789327 SNP in ARNTL/BMAL- 1, a higher prevalence of CC genotype in MS patients was evident (p- value<0.01). Variable number tandem-repeat polymorphism of the PER3 gene was also reported to accelerate disease progression in individuals predisposed to MS. This study suggests no significant association between rs6811520 polymorphism of the CLOCK gene and the risk of MS. Only one study showed the link of CC genotype of rs3789327 in ARNTL/BMAL-1 and MS risk.