Association Analysis Of MMP-2 Rs243865 And TIMP-2 Rs8179090 Polymorphisms With Chinese Moyamoya Disease

Objective: Moyamoya disease(MMD)is a rare cerebrovascular disease.This study examined whether SNPs at the MMP-2 rs243865 and the TIMP-2 rs8179090 were associated with the risk of Chinese MMD.To provide the relevant theoretical basis for the prevention and treatment of MMD.Methods: A total of 1042 Chinese Han MMD and 1060 controls were selected.The study population was divided into children with MMD(< 18 years old)and adults with MMD(≥18 years old).According to the first symptoms,the study population was divided into hemorrhagic and ischemic.Clinical data were collected and genotyped for all participants.Results: The TT frequency of MMP-2 rs243865 was lower in MMD with ischemic than that in the control group [OR=0.23,95%CI(0.07-0.79),P=0.011].Compared with the CC and CT patients,the TT genotype patients were less likely to develop ischemic [OR=0.23,95%CI(0.07-0.78),P=0.01].In patients with hemorrhagic,the frequency of allele C at TIMP-2 rs8179090 was significantly lower than that of control group [OR=0.68,95%CI(0.49-0.94),P=0.02].Compared with patients with GG genotype,patients with CC+CG genotype were less likely to develop hemorrhagic.The distribution of TT genotype frequency at MMP-2 rs243865 was different between the two groups compared with the patients with ischemic and hemorrhagic MMD(P=0.009).The frequency of CC at rs8179090 of TIMP-2 was lower in the adult with MMD than in the control group[OR=0.45,95%CI(0.24-0.83),P=0.009].Compared with GG+GC,The CC were less prone to adult MMD.The distribution of CC genotype frequency at TIMP-2 rs8179090 in children with MMD was statistically different from that in adults with MMD(P=0.002).The TT genotype frequency at MMP-2 rs243865 in children with hemorrhagic MMD was higher than that in control group [OR=10.38,95%CI(2.07-51.99),P=0.025].Compared with MMD with CC+CT genotype,pediatric MMD with TT genotype were more likely to develop hemorrhagic symptoms.Compared with the control group,the TT genotype frequency of rs243865 of MMP-2 in adult ischemic MMD was lower than that in the control group [OR=0.21,95%CI(0.05-0.92),P=0.023].Compared with the patients with CC+CT,adult patients with TT were less likely to develop the hemorrhagic symptoms.(P=0.020).At rs8179090 of TIMP-2,the frequency of CC genotype in adult ischemic MMD was lower than that in control group [OR=0.40,95%CI(0.18-0.86),P=0.015].Compared with patients with GG+GC,adult patients with CC were less likely to develop ischemia symptoms.The frequency of adult hemorrhagic MMD allele C was lower than that of control group [OR=0.61,95%CI(0.43-0.87),P=0.006].Compared with patients with GG,adult patients with CC+GC were less likely to develop hemorrhagic symptoms.Conclusion: 1.The polymorphism of the MMP-2 rs243865 may be a protective factor for ischemic MMD in Chinese Han population,especially related to reducing the risk of ischemic MMD in Chinese Han adults.2.The polymorphism of TIMP-2 rs8179090 may be a protective factor for MMD in Chinese Han,especially related to the reduction of the risk of ischemic and hemorrhagic MMD in Chinese Han adults.