Association between matrix metalloproteinase-3 gene polymorphism and moyamoya disease

Ma, Junpeng; You, Chao

doi:10.1016/j.jocn.2014.08.034

Cited by 7 publications

(7 citation statements)

References 27 publications

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“…In line with the observation of a differential expression of these ECM remodeling enzymes between patients' and controls' biological samples, some studies showed an association of MMD with polymorphisms located in of TIMP2, MMP2, MMP3 genes or in their promoters [75][76][77][78] . Again, conflicting results between studies did not allow any conclusions to be drawn about the significance of these associations [73,79,80] .…”

Section: Genome-wide Linkage Studiesmentioning

confidence: 68%

Research Progresses in Understanding the Pathophysiology of Moyamoya Disease

et al. 2016

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Background: The pathogenesis of moyamoya disease (MMD) is still unknown. The detection of inflammatory molecules such as cytokines, chemokines and growth factors in MMD patients' biological fluids supports the hypothesis that an abnormal angiogenesis is implicated in MMD pathogenesis. However, it is unclear whether these anomalies are the consequences of the disease or rather causal factors as well as these mechanisms remain insufficient to explain the pathophysiology of MMD. The presence of a family history in about 9-15% of Asian patients, the highly variable incidence rate between different ethnic and sex groups and the age of onset support the role of genetic factors in MMD pathogenesis. However, although some genetic loci have been associated with MMD, few of them have been replicated in independent series. Recently, RNF213 gene was shown to be strongly associated with MMD occurrence with a founder effect in East Asian patients. However, the mechanisms leading from RNF213 mutations to MMD clinical features are still unknown. Summary: The research on pathogenic mechanism of MMD is in its infancy. MMD is probably a complex and heterogeneous disorder, including different phenotypes and genotypes, in which more than a single factor is implicated. Key Message: Since the diagnosis of MMD is rapidly increasing worldwide, the development of more efficient stratifying risk systems, including both clinical but also biological drivers became imperative to improve our ability of predict prognosis and to develop mechanism-tailored interventions.

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Section: Genome-wide Linkage Studiesmentioning

confidence: 68%

Research Progresses in Understanding the Pathophysiology of Moyamoya Disease

et al. 2016

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“…An imbalance leads to vascular smooth muscle hyperplasia and thickening, thus leading to vascular stenosis, one of the key pathogenic factors responsible for MMD [8]. Studies have shown that the 1171 (6A/6A) mutation in the MMP3 gene is associated with a risk of MMD and that the risk of the (6A/6A) genotype is higher than that of the (5A/6A) genotype [52][53][54].…”

Section: Discussionmentioning

confidence: 99%

The Association Between RNF213 , MMP3 , and Moyamoya Disease: Screening the Full Exons of Susceptibility Genes in Families with Moyamoya Disease

Xiao

Liu

et al. 2021

Preprint

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Background: In this study, we aimed to investigate the association between polymorphisms in the RNF213 and MMP3 genes and Moyamoya disease (MMD) and to screen susceptibility genes for families with MMD.Methods: The mutation of RNF213 gene (rs112735431,rs148731719) and MMP3 gene rs3025058 were detected by first generation sequencing and CRISPR-Cas12a. The genetic susceptibility genes of MMD families samples were studied by whole exome sequencing (WES). Results: The application of CRISPR-Cas12a and Sanger sequencing identified rs112735431 and rs148731719 mutations in the RNF213 gene, and an insertion mutation in the MMP3 gene (rs3025058) with significant regional differences (P<0.05). Additionally, we identified 100% agreement between CRISPR-Cas12a and Sanger sequencing with regards to the detection of these mutations in samples, thus indicating that CRISPR-Cas12a can be used for the detection of MMD mutations. Next, we carried out whole exon screening for family members with MMD and identified multiple recessive genes associated with genetic disease. Notably, the Titin (TTN) gene (rs771533925, rs559712998 and rs72677250) was significantly associated with point mutations. Screening of the Exome Aggregation Consortium (EXAC) database identified significant differences between these populations with respect to frequency. PROVEAN，nvariant Feature Transform (SIFT) and PolyPhen algorithms further demonstrated that rs771533925 and rs72677250 were potentially damaging in three databases, rs559712998 was considered to be tolerated in above mentioned databases. Scale Invariant Feature Transform (SIFT) and PolyPhen algorithms further demonstrated that rs771533925 and rs72677250 were potentially damaging by all three databases and that rs559712998 was considered to be tolerated in above mentioned databases. Gene Ontology (GO) analysis demonstrated that the target of TTN is involved in many important biological processes. The screening of 50 sporadic MMD samples failed to identify any mutations, thus indicating that single nucleotide polymorphism (SNP) mutation sites (rs771533925, rs559712998, and rs72677250) within the TTN gene may play an important role in the inheritance of MMD. Conclusions: In summary, our study investigated susceptibility genes for MMD from multiple perspectives and found that CRISPR-Cas12a technology can efficiently detect MMD mutation sites. Our findings provide a theoretical basis for future investigations of the molecular mechanisms that underlie MMD.

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“…This meta-analysis revealed that one copy of the 6A allele significantly increases the risk of MMD (OR = 1.64, 95% confidence interval 1.26–2.13, p = 0.0002). Moreover, the risk of MMD was higher in the 6A/6A genotype than in the genotypes of 6A/5A and 5A/5A (OR = 1.79, 95% confidence interval 1.32–2.42, p = 0.0002) [ 90 ]. Recently, Wang et al published a meta-analysis, evaluating seven polymorphisms in 4711 MMD patients and 8704 controls in 24 studies.…”

Section: Genetic Association Studies and Sequencingmentioning

confidence: 99%

The Genetic Basis of Moyamoya Disease

Mertens

Graupera

Gerhardt

et al. 2021

Transl. Stroke Res.

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Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive spontaneous bilateral occlusion of the intracranial internal cerebral arteries (ICA) and their major branches with compensatory capillary collaterals resembling a “puff of smoke” (Japanese: Moyamoya) on cerebral angiography. These pathological alterations of the vessels are called Moyamoya arteriopathy or vasculopathy and a further distinction is made between primary and secondary MMD. Clinical presentation depends on age and population, with hemorrhage and ischemic infarcts in particular leading to severe neurological dysfunction or even death. Although the diagnostic suspicion can be posed by MRA or CTA, cerebral angiography is mandatory for diagnostic confirmation. Since no therapy to limit the stenotic lesions or the development of a collateral network is available, the only treatment established so far is surgical revascularization. The pathophysiology still remains unknown. Due to the early age of onset, familial cases and the variable incidence rate between different ethnic groups, the focus was put on genetic aspects early on. Several genetic risk loci as well as individual risk genes have been reported; however, few of them could be replicated in independent series. Linkage studies revealed linkage to the 17q25 locus. Multiple studies on the association of SNPs and MMD have been conducted, mainly focussing on the endothelium, smooth muscle cells, cytokines and growth factors. A variant of the RNF213 gene was shown to be strongly associated with MMD with a founder effect in the East Asian population. Although it is unknown how mutations in the RNF213 gene, encoding for a ubiquitously expressed 591 kDa cytosolic protein, lead to clinical features of MMD, RNF213 has been confirmed as a susceptibility gene in several studies with a gene dosage-dependent clinical phenotype, allowing preventive screening and possibly the development of new therapeutic approaches. This review focuses on the genetic basis of primary MMD only.

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Association between matrix metalloproteinase-3 gene polymorphism and moyamoya disease

Cited by 7 publications

References 27 publications

Research Progresses in Understanding the Pathophysiology of Moyamoya Disease

Research Progresses in Understanding the Pathophysiology of Moyamoya Disease

The Association Between RNF213 , MMP3 , and Moyamoya Disease: Screening the Full Exons of Susceptibility Genes in Families with Moyamoya Disease

The Genetic Basis of Moyamoya Disease

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