With a feature of complex pathogenic mechanisms, migraine is a well-known common neurovascular disorder. Multiple genes are responsible for hindering the susceptibility of pain threshold one of which is the eNOS gene and its variants. Multiple independent observational studies with case–control design produced conflicting findings, which can be attributed to a variety of factors including varying sample sizes, demographic stratification, technique application, etc. Therefore, in the present study we aimed to find out the precise risk between the selected variant of eNOS and the risk of migraine and its clinical subtypes using a meta-analysis approach. To find the association between the risk variants of the eNOS gene and migraine, a PRISMA-based systematic literature review strategy was utilized to search via online resources including PubMed and Google Scholar. Using several genetic models, odds ratios with 95% confidence intervals were computed to pool the data. To access heterogeneity, Cochran's Q Test and I2 statistics were utilized, while Begg's and Egger's tests were used to determine publication bias. A p-value of 0.05 or below was deemed statistically significant for all two-sided tests. The present meta-analysis was able to find out the significant protective association between rs743506 and migraine after using dominant (OR: 0.66, CI [0.49–0.86]), over-dominant (OR: 0.56, CI [0.42–0.75]), codominant model (OR: 0.58, CI[0.43–0.77]). Only significant risk association was found between rs1799983, rs3918226, and risk of migraine with aura after utilizing recessive and codominant models i.e., HR vs HW and HR vs HT. The present meta-analysis showed that rs743506 showed a protective association in comparison to rs1799983, rs3918226 which showed significant risk in the MA group. Also, TSA showed non-significant results and therefore, in conclusion, more studies are required to establish risk.

Graphical Abstract

中文翻译：

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eNOS 的 -786 T > C、+ 884 G > A、VNTR、rs743506、rs3918226 与偏头痛易感性之间风险关联的全面调查：利用试验序贯分析的更新荟萃分析

偏头痛是一种众所周知的常见神经血管疾病，其发病机制复杂。多个基因负责阻碍疼痛阈值的敏感性，其中之一是eNOS基因及其变体。采用病例对照设计的多项独立观察性研究产生了相互矛盾的结果，这可归因于多种因素，包括不同的样本量、人口分层、技术应用等。因此，在本研究中，我们的目的是找出两者之间的精确风险使用荟萃分析方法确定eNOS的选定变体以及偏头痛及其临床亚型的风险。为了找到eNOS基因的风险变异与偏头痛之间的关联，我们利用基于 PRISMA 的系统文献综述策略通过 PubMed 和 Google Scholar 等在线资源进行搜索。使用多种遗传模型，计算具有 95% 置信区间的比值比来汇集数据。为了了解异质性，使用了 Cochran 的 Q 检验和 I2 统计数据，同时使用 Begg 和 Egger 的检验来确定发表偏倚。对于所有双边测试，0.05 或以下的 p 值被认为具有统计显着性。本荟萃分析能够在使用显性（OR：0.66，CI [0.49–0.86]）、过度显性（OR：0.56，CI [0.42–0.75]）、共显性模型（OR：0.58，CI[0.43–0.77]）。在利用隐性和共显性模型（即 HR 与 HW 和 HR 与 HT）后，仅发现 rs1799983、rs3918226 与先兆偏头痛风险之间存在显着风险关联。目前的荟萃分析表明，与 rs1799983、rs3918226 相比，rs743506 显示出保护性关联，而 rs1799983、rs3918226 在 MA 组中显示出显着风险。此外，TSA 显示的结果并不显着，因此总而言之，需要更多的研究来确定风险。

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