title: Impacts and interactions of PDGFRB, MMP-3, TIMP-2, and RNF213 polymorphisms on the risk of Moyamoya disease in Han Chinese human subjects.
abstract: 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.
authors.affiliation: Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu Province, PR China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Wang
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Wenhua
authors.initials: W
authors.lastname: Liu
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Xiong
authors.forename: Wen
authors.initials: W
authors.lastname: Sun
authors.forename: Xianjun
authors.initials: X
authors.lastname: Huang
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Jiang
authors.forename: Guanzhong
authors.initials: G
authors.lastname: Ni
authors.forename: Wenshan
authors.initials: W
authors.lastname: Sun
authors.forename: Lulu
authors.initials: L
authors.lastname: Zhou
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.forename: Wusheng
authors.initials: W
authors.lastname: Zhu
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Liu
authors.forename: Gelin
authors.initials: G
authors.lastname: Xu
mesh_terms: D000251:Adenosine Triphosphatases; D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D004843:Epistasis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D008875:Middle Aged; D009072:Moyamoya Disease / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D019716:Tissue Inhibitor of Metalloproteinase-2; C557998:RNF213 protein, human; D044767:Ubiquitin-Protein Ligases; D020797:Receptor, Platelet-Derived Growth Factor beta; D019278:Matrix Metalloproteinase 3; D000251:Adenosine Triphosphatases
keywords: Genetic association studies; MDR; MMD; MMP-3; Moyamoya disease; Multifactor dimensionality reduction; PDGFRB; RNF213; Single nucleotide polymorphisms; TGFB1; TIMP-2; eNOS; endothelial nitric oxide synthase; matrix metalloproteinase-3; multifactor dimensionality reduction; platelet derived growth factor receptor beta; ring finger 213; tissue inhibitors of metalloproteinase-2; transforming growth factor beta 1