{
  "abstract": "Background: Multiple Sclerosis (MS) is an inflammatory neurodegenerative disease with incompletely understood aetiology beyond the HLA-DRB1 locus. Mitochondrial haplogroup U, prevalent in Middle Eastern and Near Eastern populations, encodes functional variants in NADH dehydrogenase subunits associated with elevated reactive oxygen species (ROS) production. A 2022 study (Al-Kafaji et al., PLoS ONE) reported a nominal association between haplogroup U and RRMS in Saudi Arab patients (OR 6.26; 95% CI 0.82–48.10) in a single, small (n = 47) cohort. We conducted a systematic review and meta-analysis to determine whether this signal is supported by independently verifiable case-control data from other Arab or Near Eastern populations.\n\nMethods: PRISMA 2020 systematic review. PubMed/MEDLINE was searched to 15 July 2026 using a concept-level strategy – (“mitochondrial DNA”[tiab] OR “mtDNA”[tiab] OR “DNA, Mitochondrial”[MeSH] OR “Mitochondria”[MeSH]) AND (“haplogroup”[tiab] OR “haplogroups”[tiab] OR “haplotype”[tiab]) AND (“multiple sclerosis”[tiab] OR “Multiple Sclerosis”[MeSH] OR “demyelinating”[tiab] OR “RRMS”[tiab]) – with no population terms applied at the search stage; population eligibility (Arab or Near Eastern cohort) was assessed during screening rather than baked into the search string, to maximise sensitivity. Eligible studies were case-control studies reporting mitochondrial haplogroup U frequency in MS cases versus healthy controls in an Arab or Near Eastern population, with data sufficient to construct a 2 × 2 table. Odds ratios were pooled using a fixed-effect inverse-variance model.\n\nResults: The search identified 30 records. After screening and full-text assessment, two studies met full inclusion criteria for quantitative pooling: Al-Kafaji et al. [1] (Saudi Arabia, n = 47) and Hassani-Kumleh et al. [2] (Iran, n = 154); total pooled N = 201 (77 MS cases, 124 controls). The fixed-effect pooled OR was 4.11 (95% CI 1.25–13.55; p = 0.020), with no meaningful heterogeneity (I²=0%, Cochran’s Q = 0.25, df = 1). Two further Near Eastern studies (Houshmand et al. [3]; Ghabaee et al. [4]) reported related but non-poolable data – haplogroup J association and a haplogroup U case-series prevalence without a control arm, respectively – and are discussed narratively.\n\nConclusions: Across two independently verified Near Eastern case-control cohorts, mitochondrial haplogroup U is significantly associated with increased MS risk (pooled OR 4.11, 95% CI 1.25–13.55). The evidence base remains small, and the wide confidence interval reflects this. A larger, prospective, adequately powered study in Arab and Near Eastern MS cohorts is needed to confirm and refine this association.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12883-026-05223-7.",
  "abstract_shown": true,
  "affiliations": [
    "Bahçeşehir Cyprus University, North, Cyprus. 20156985@std.neu.edu.tr.",
    "Sankofa Research and Mentorship Hub, Buea, Cameroon. 20156985@std.neu.edu.tr."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Ibrahim Ibrahim Shuaibu",
      "orcid": "0000-0003-1103-3150"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8j9y101a38qaa.bib",
  "cited_by": 0,
  "doi": "10.1186/s12883-026-05223-7",
  "fulltext_url": "https://europepmc.org/articles/PMC13726032",
  "id": "8j9y101a38qaa",
  "issns": [
    "1471-2377"
  ],
  "landing_url": "https://europepmc.org/article/MED/42968057",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2734|Multiple Sclerosis Research Studies"
    ]
  ],
  "openalex": "W7172422518",
  "pdf_url": "https://europepmc.org/articles/PMC13726032?pdf=render",
  "pmcid": "PMC13726032",
  "pmid": "42968057",
  "published": "2026-08-05",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/8j9y101a38qaa.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T15:20:54Z",
      "native_id": "MED:42968057",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42968057"
    },
    {
      "first_seen": "2026-11-05T12:22:27Z",
      "native_id": "PMC13726032",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s12883-026-05223-7"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2734|Multiple Sclerosis Research Studies",
      "subfield": "general"
    }
  ],
  "title": "Mitochondrial Haplogroup U and multiple sclerosis risk in Arab and Near Eastern populations: a systematic review and meta-analysis.",
  "title_text": "Mitochondrial Haplogroup U and multiple sclerosis risk in Arab and Near Eastern populations: a systematic review and meta-analysis.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:22:05Z",
  "url": "https://research.draconitic.com/paper/8j9y101a38qaa",
  "venue": "BMC neurology",
  "versions": []
}