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Background <p>Multiple sclerosis (MS) is still under investigation for its pathogenesis. This study explores the relationship between the key circadian rhythm regulators’ genes, <i>ARNTL/BMAL-1</i> and <i>CLOCK</i>, and MS pathogenesis.</p> Methods <p>Following the PRISMA2020 statement, a systematic search was conducted in PubMed, Scopus, Embase, and Web of Science for studies published up to July 2024. Clinical studies concerning the role of circadian genes in MS pathogenesis were considered for inclusion. The risk of bias was assessed using the JBI critical appraisal tools, and Comprehensive Meta-Analysis (CMA4) was utilized for the quantitative synthesis.</p> Result <p>Out of 537 results of the database searches, four studies were included. The total sample size of the included studies was 4010 (2110 MS cases and 1900 controls). CT genotype in rs6811520 in the <i>CLOCK</i> gene is suggested as a risk factor for MS in the Iranian population; however, there was no noteworthy association with rs3789327 in the <i>ARNTL/BMAL-1</i> gene in this population. In individuals of Slavic origin, the CC genotype in both rs3789327 in the <i>ARNTL/BMAL-1</i> gene and rs6811520 in the <i>CLOCK</i> gene was reported as a genetic risk factor for MS. In contrast, there was no association between MS status and genotypes of rs3789327 in the <i>ARNTL/BMAL-1</i> gene and rs6811520 in the <i>CLOCK</i> gene in Caucasians of Spanish origin. In the Egyptian population, a higher prevalence of the TT genotype in MS patients was found in rs6811520 in the <i>CLOCK</i> gene. In the quantitative synthesis, no significant statistical relationship was found between MS pathogenesis regarding rs6811520 in the <i>CLOCK</i> gene and rs3789327 in the <i>ARNTL/BMAL-1</i> gene (<i>p</i>-values &gt; 0.05).</p> Conclusion <p>Based on the limited available evidence, there may be an ethnic-specific association between <i>ARNTL/BMAL-1</i> and <i>CLOCK</i> gene and MS susceptibility; however, considering the limitations such as the small number of included studies and small sample sizes, future multiethnic studies are needed on this topic.</p>

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Polymorphisms in CLOCK and ARNTL/BMAL-1 genes in multiple sclerosis: a systematic review and meta-analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月6日

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  • Mobina Oladghaffari,
  • Heliya Bandehagh,
  • Fatemeh Malekinejad,
  • Shahrzad Fakhkhari,
  • Narges Koohi,
  • Seyedehyasmin Moghaddamziabari,
  • Sina Hamzehzadeh,
  • Elahe Mohammadian,
  • Mahnaz Talebi,
  • Hanieh Salehi-pourmehr,
  • Amirreza Naseri

摘要

Background

Multiple sclerosis (MS) is still under investigation for its pathogenesis. This study explores the relationship between the key circadian rhythm regulators’ genes, ARNTL/BMAL-1 and CLOCK, and MS pathogenesis.

Methods

Following the PRISMA2020 statement, a systematic search was conducted in PubMed, Scopus, Embase, and Web of Science for studies published up to July 2024. Clinical studies concerning the role of circadian genes in MS pathogenesis were considered for inclusion. The risk of bias was assessed using the JBI critical appraisal tools, and Comprehensive Meta-Analysis (CMA4) was utilized for the quantitative synthesis.

Result

Out of 537 results of the database searches, four studies were included. The total sample size of the included studies was 4010 (2110 MS cases and 1900 controls). CT genotype in rs6811520 in the CLOCK gene is suggested as a risk factor for MS in the Iranian population; however, there was no noteworthy association with rs3789327 in the ARNTL/BMAL-1 gene in this population. In individuals of Slavic origin, the CC genotype in both rs3789327 in the ARNTL/BMAL-1 gene and rs6811520 in the CLOCK gene was reported as a genetic risk factor for MS. In contrast, there was no association between MS status and genotypes of rs3789327 in the ARNTL/BMAL-1 gene and rs6811520 in the CLOCK gene in Caucasians of Spanish origin. In the Egyptian population, a higher prevalence of the TT genotype in MS patients was found in rs6811520 in the CLOCK gene. In the quantitative synthesis, no significant statistical relationship was found between MS pathogenesis regarding rs6811520 in the CLOCK gene and rs3789327 in the ARNTL/BMAL-1 gene (p-values > 0.05).

Conclusion

Based on the limited available evidence, there may be an ethnic-specific association between ARNTL/BMAL-1 and CLOCK gene and MS susceptibility; however, considering the limitations such as the small number of included studies and small sample sizes, future multiethnic studies are needed on this topic.