Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu Province, PR China.
Gene. 2013 Sep 10;526(2):437-42. doi: 10.1016/j.gene.2013.05.083. Epub 2013 Jun 12.
Polymorphisms of PDGFRB, MMP-3, TIMP-2, RNF213, TGFB1, Raptor and eNOS genes have been associated with Moyamoya disease (MMD) separately in studies, but their interactions on MMD have never been evaluated in one study. This study enrolled 96 MMD patients and 96 controls to evaluate the contributions and interactions of these polymorphisms on MMD in Chinese Hans. After genotyping, five polymorphisms loci were deemed suitable for analysis, rs3828610 in PDGFRB, rs3025058 in MMP-3, rs8179090 in TIMP-2, rs112735431 and rs148731719 in RNF213. Interactions of different loci on MMD were evaluated by multifactor dimensionality reduction (MDR) method. Significantly higher frequencies of A allele and G/A genotype of rs112735431 in RNF213 were observed in MMD patients compared with controls (P=0.011; P=0.018, respectively). In the dominant model, G/A genotype of rs112735431 was associated with increased risk of MMD (P=0.018). A higher frequency of G allele and G/G genotype of rs148731719 in RNF213 gene in patient than control group (P<0.001; P<0.01, respectively) was also detected. No significant association between MMD and other three loci (P>0.05) was detected. MDR analysis failed to detect any significant interaction among these five loci in the occurrence of MMD (P>0.05), but the combination of three loci (rs112735431 in RNF213, rs3828610 in PDGFRB, rs3025058 in MMP-3) could have the maximum testing accuracy (57.29%) and cross-validation consistency (10/10). The results indicated that RNF213 rs112735431 and rs148731719 may exert a significant influence on MMD occurrence. Compared with this overwhelming effect, the influences of PDGFRB, MMP-3, and TIMP-2 on MMD may be unremarkable in Chinese Hans. There may be no prominent interaction among these five gene polymorphisms on the occurrence of MMD.
PDGFRB、MMP-3、TIMP-2、RNF213、TGFB1、Raptor 和 eNOS 基因的多态性已分别在研究中与烟雾病（MMD）相关，但在一项研究中从未评估过它们在 MMD 中的相互作用。本研究纳入 96 例 MMD 患者和 96 例对照，以评估这些多态性在中国汉族人群中对 MMD 的贡献和相互作用。基因分型后，有 5 个多态性位点被认为适合分析，即 PDGFRB 中的 rs3828610、MMP-3 中的 rs3025058、TIMP-2 中的 rs8179090、RNF213 中的 rs112735431 和 rs148731719。采用多因子降维（MDR）方法评估不同位点对 MMD 的相互作用。结果显示，与对照组相比，rs112735431 中的 RNF213 等位基因 A 和 G/A 基因型在 MMD 患者中明显更高（P=0.011；P=0.018）。在显性模型中，rs112735431 的 G/A 基因型与 MMD 风险增加相关（P=0.018）。在患者组中，RNF213 基因中 rs148731719 的 G 等位基因和 G/G 基因型的频率高于对照组（P<0.001；P<0.01）。其他三个位点（P>0.05）与 MMD 之间没有明显的关联。MDR 分析未能检测到这些五个位点在 MMD 发生中的任何显著相互作用（P>0.05），但三个位点（RNF213 中的 rs112735431、PDGFRB 中的 rs3828610、MMP-3 中的 rs3025058）的组合可能具有最大的测试准确性（57.29%）和交叉验证一致性（10/10）。结果表明，RNF213 rs112735431 和 rs148731719 可能对 MMD 的发生有显著影响。与这种压倒性的影响相比，PDGFRB、MMP-3 和 TIMP-2 对 MMD 的影响在中国汉族人群中可能不明显。这五个基因多态性在 MMD 的发生中可能没有明显的相互作用。
