Genotyping of ARNTL and CLOCK Circadian Rhythm Gene Polymorphisms in Iranian Patients with Multiple Sclerosis

Abstract

Background: Multiple sclerosis (MS) is a central nervous system disease accompanied by variable symptoms such as optic neuritis, fatigue, spasticity, neuro-urological dysfunction, paresthesia, and headache. The frequency of MS was reported differently in geographical latitude, which may be in relation to genetic changes in circadian rhythm regulator genes, including aryl hydrocarbon receptor nuclear translocator-like (ARNTL) and circadian locomotor output cycles kaput (CLOCK). Objectives: This study aimed at genotyping rs3789327 in the ARNTL and rs6811520 in the CLOCK genes and their association with MS in the Iranian population. Methods: Totally, 100 patients with relapsing-remitting multiple sclerosis (RRMS) and 100 healthy controls were recruited. DNA extracted from the whole blood of all patients was genotyped by high-resolution melting (HRM) real-time PCR method for the rs3789327 and rs6811520 within the ARNTL and CLOCK genes, respectively, then the HRM results were confirmed by Sanger sequencing method. Results: Our results showed a statistically significant difference in genotype distributions in the CLOCK gene (rs6811520, P = 0.023) in MS and healthy controls, but in the ARNTL gene, there was no significant change in rs3789327 genotypic distribution between MS patients and healthy individuals (P = 0.2). The TC genotype of the rs6811520 was associated with a higher risk for MS [P = 0.006, OR = 4.164, 95% confidence intervals (CI) 1.43 - 12.09]. Conclusions: The present results suggested that genetic variations in the CLOCK gene are a risk factor for MS.