Department of Neurology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fijian, China.
Department of Acupuncture and Moxibustion, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fijian, China.
Brain Behav. 2022 Feb;12(2):e2473. doi: 10.1002/brb3.2473. Epub 2022 Jan 5.
To investigate the association of eight variants of four matrix metalloproteinase (MMP) genes with ischemic stroke (IS) and whether interactions among these single nucleotide polymorphisms (SNPs) increases the risk of IS.
Among 547 patients with ischemic stroke and 350 controls, matrix-assisted laser desorption/ionization time of flight mass spectrometry was used to examine eight variants arising from four different genes, including MMP-1 (rs1799750), MMP-2 (rs243865, rs2285053, rs2241145), MMP-9 (rs17576), and MMP-12 (rs660599, rs2276109, and rs652438). Gene-gene interactions were employed using generalized multifactor dimensionality reduction (GMDR) methods.
The frequency of rs17576 was significantly higher in IS patients than in controls (p = .033). Logistic regression analysis revealed the AG and GG genotypes of rs17576 to be associated with a higher risk for IS, with the odds ratio and 95% confidence interval being 2.490 (1.251-4.959) and 2.494 (1.274-4.886), respectively. GMDR analysis showed a significant SNP-SNP interaction between rs17576 and rs660599 (the testing balanced accuracy was 53.70% and cross-validation consistency was 8/10, p = .0107). Logistic regression analysis showed the interaction between rs17576 and rs660599 to be an independent risk factor for IS with an odds ratio of 1.568 and a 95% confidence interval of 1.152-2.135.
An MMP-9 rs17576 polymorphism is associated with increased IS risk in the Han Hakka population and interaction between MMP-9 rs17576 and MMP-12 rs660599 is associated with increased IS risk as well.
研究四种基质金属蛋白酶（MMP）基因的 8 种变体与缺血性脑卒中（IS）的关联，以及这些单核苷酸多态性（SNP）之间的相互作用是否会增加 IS 的风险。
在 547 名缺血性脑卒中患者和 350 名对照中，采用基质辅助激光解吸/电离飞行时间质谱法检测来自四个不同基因的 8 种变体，包括 MMP-1（rs1799750）、MMP-2（rs243865、rs2285053、rs2241145）、MMP-9（rs17576）和 MMP-12（rs660599、rs2276109 和 rs652438）。使用广义多因子降维（GMDR）方法研究基因-基因相互作用。
IS 患者 rs17576 的频率明显高于对照组（p=0.033）。Logistic 回归分析显示 rs17576 的 AG 和 GG 基因型与 IS 风险增加相关，优势比和 95%置信区间分别为 2.490（1.251-4.959）和 2.494（1.274-4.886）。GMDR 分析显示 rs17576 与 rs660599 之间存在显著的 SNP-SNP 相互作用（检验平衡准确性为 53.70%，交叉验证一致性为 8/10，p=0.0107）。Logistic 回归分析显示 rs17576 与 rs660599 之间的相互作用是 IS 的一个独立危险因素，优势比为 1.568，95%置信区间为 1.152-2.135。
在汉族客家人中，MMP-9 rs17576 多态性与 IS 风险增加相关，MMP-9 rs17576 与 MMP-12 rs660599 之间的相互作用也与 IS 风险增加相关。
