Associations of matrix metalloproteinase-9 and tissue inhibitory factor-1 polymorphisms with Parkinson disease in Taiwan

Matrix metalloproteinases (MMPs) function in the degradation of extracellular matrix and are considered to play a role in the pathogenesis of neurodegenerative diseases including Parkinson disease (PD). MMPs activities are modulated by tissue inhibitors of metalloproteinases (TIMPs). This study examined whether the genetic polymorphisms of MMP-3, gelatinase (MMP-2 and MMP-9), TIMP-2, and TIMP-1 were associated with PD in Taiwan. A total of 359 PD patients and 332 controls were enrolled. The candidate genetic variants included MMP-2 rs2285053 (-735 C>T), MMP-3 rs3025058 (-1171 5A>6A), MMP-9 rs3918241 (-1831 T>A), rs17576 (G>A, R279Q), and rs3787268 (G>A, intron), TIMP-1 rs4898 (T>C, F124F), and TIMP-2 rs7503607 (-269 G>T). Associations were tested by logistic regression, adjusted with gender and age at onset. Minor allele frequency of TIMP-1 rs4898 (36.0%) was significantly lower in the male PD patients than in the male controls (51.2%) (x2 test, P=0.004). When adjusted with gender and age at onset, MMP-9 rs17576 AA genotype was associated with PD susceptibility in a recessive fashion (odds ratios [OR]=2.28, 95% confidence intervals [95% CI]=1.12-4.62, P=0.02). In males, TIMP-1 rs4898C allele was associated with a protective effect on PD (OR=0.75, 95% CI=0.60-0.94, P=0.014). We did not find association between the examined genetic variants of MMP-2, MMP-3, and TIMP-2 and PD susceptibility. This is the first study that demonstrated a protective effect of TIMP-1 rs4898C allele on male PD and a modest association of MMP-9 rs17576 AA genotype with PD susceptibility in the Taiwan population. Further replication is needed for confirmation.