Mitochondrial Haplogroup U and multiple sclerosis risk in Arab and Near Eastern populations: a systematic review and meta-analysis.
- 1Bahçeşehir Cyprus University, North, Cyprus. [email protected].
- 2Sankofa Research and Mentorship Hub, Buea, Cameroon. [email protected].
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.
Methods: 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.
Results: 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.
Conclusions: 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.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12883-026-05223-7.
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BibTeX
@article{shuaibu2026mitochondrial,
title = {{Mitochondrial Haplogroup U and multiple sclerosis risk in Arab and Near Eastern populations: a systematic review and meta-analysis.}},
author = {Ibrahim Ibrahim Shuaibu},
journal = {BMC neurology},
year = {2026},
month = aug,
doi = {10.1186/s12883-026-05223-7},
url = {https://europepmc.org/article/MED/42968057},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Mitochondrial Haplogroup U and multiple sclerosis risk in Arab and Near Eastern populations: a systematic review and meta-analysis.
AU - Ibrahim Ibrahim Shuaibu
PY - 2026
DA - 2026/08/05
JO - BMC neurology
DO - 10.1186/s12883-026-05223-7
UR - https://europepmc.org/article/MED/42968057
AB - 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. Methods: 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. Results: 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. Conclusions: 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. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12883-026-05223-7.
SN - 1471-2377
ER -