engleski

Circadian rhythm genes and multiple sclerosis (MS).

Evidence from epidemiological studies indicates, that, prevalence of MS varies with geographic latitude, increasing with distance from the equator on both hemispheres. We hypothesized that explanation for the latitude effect might be related to sun exposure which has been shown to impact internal circadian rhythm. This rhytm is controlled by circadian rhythm genes and that could therefore affect MS susceptibility. A total of 826 Caucasian patients and 888 healthy unrelated ethnically matched controls without family history of MS, were included in the study. In patients, the diagnosis of MS was established according to McDonald’s criteria. Altogether, 8 SNP were included in our study, 4 in CLOCK gene: rs6811520, rs6850524, rs11932595 and rs13124436 ; and 4 in ARNTL gene: 3789327, rs1481892, rs4757144 and rs12363415. The significance of association for individual SNPs was analyzed using the Chi-Square test (χ2). Odds ratios (OR) and their respective 95% confidence intervals(CI) was also calculated to compare the allelic frequency and genotype distribution in patients and control subjects. Significant difference in distribution of ARNTL rs3789327 polymorphism genotypes was found in patients with MS in comparison to controls, with P-value of 4.6e-07 and odds ratio equal to 0.56 (95% CI: 0.45-0.71).Other SNPs in ARNTL and CLOCK genes did not display significant association with MS susceptibility. We provide evidence for association between genetic variation in ARNTL gene and multiple sclerosis. Further studies will be required to substantiate the significance of these genetic variations.

multiple sclerosis; CLOCK gene; ARNTL gene

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