线粒体单倍群U与阿拉伯及近东人群的多发性硬化风险：一项系统综述与荟萃分析。
完整摘要 · 中文译文
背景：多发性硬化（MS）是一种炎症性神经退行性疾病，其病因除HLA-DRB1位点外尚未完全阐明。线粒体单倍群U在中东和近东人群中常见，其编码的NADH脱氢酶亚基功能变异与活性氧（ROS）生成升高相关。2022年一项研究（Al-Kafaji等，PLoS ONE）在一个单一的小型队列（n = 47）中报告，单倍群U与沙特阿拉伯患者的复发缓解型多发性硬化（RRMS）存在名义关联（OR 6.26；95% CI 0.82-48.10）。我们进行了一项系统综述和荟萃分析，以确定该信号是否得到来自其他阿拉伯或近东人群的可独立验证的病例对照数据的支持。 方法：PRISMA 2020系统综述。检索PubMed/MEDLINE至2026年7月15日，采用概念层面检索策略——（“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]）——检索阶段未应用人群术语；人群合格性（阿拉伯或近东队列）在筛选阶段进行评估，而非嵌入检索字符串，以最大化灵敏度。合格研究为病例对照研究，报告阿拉伯或近东人群中MS病例与健康对照的线粒体单倍群U频率，且数据足以构建2 × 2表。采用固定效应逆方差 方差模型。 结果：检索共识别出30条记录。经过筛选和全文评估，两项研究符合定量合并的完整纳入标准：Al-Kafaji等[1]（沙特阿拉伯，n = 47）和Hassani-Kumleh等[2]（伊朗，n = 154）；总合并N = 201（77例MS病例，124例对照）。固定效应合并OR为4.11（95% CI 1.25-13.55；p = 0.020），无有意义的异质性（I²=0%，Cochran's Q = 0.25，df = 1）。另外两项近东研究（Houshmand等[3]；Ghabaee等[4]）报告了相关但无法合并的数据——分别为单倍群J关联和无对照组的单倍群U病例系列患病率——以叙述性方式讨论。 结论：在两项独立验证的近东病例对照队列中，线粒体单倍群U与MS风险增加显著相关（合并OR 4.11，95% CI 1.25-13.55）。证据基础仍然较小，较宽的置信区间反映了这一点。需要在阿拉伯和近东MS队列中开展更大规模、前瞻性、具有足够把握度的研究，以确认和完善这一关联。
完整摘要 · 英文原文
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.