Association of a Functional Polymorphism in the MMP-3 Gene with Moyamoya Disease in the Chinese Han Population

Abstract

Background: Moyamoya disease (MMD) is an uncommon cerebrovascular disease characterized by progressive stenosis of the intracranial internal carotid arteries and their proximal branches. The important role of genetic factors in the etiology and pathogenesis of MMD is being increasingly recognized. The study was designed to examine the association of single nucleotide polymorphisms in matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinase (TIMP) genes with MMD occurrence. Methods: A case-control study was performed. Five functional promoter polymorphisms in the MMP-2, MMP-3, MMP-9 and MMP-13 genes and a potentially functional promoter polymorphism in the TIMP-2 gene were determined by polymerase chain reaction-restriction fragment length polymorphism. Their associations with MMD were analyzed by multivariate logistic regression. Results: In total, 208 definite patients with MMD (including 31 familial MMD, FMMD, patients) and 224 healthy subjects were recruited. The frequency of the MMP-3 5A/6A and 5A/5A genotypes was significantly lower in MMD patients (OR = 0.57, 95% CI 0.38–0.86, p_corr = 0.042) compared with healthy controls in a dominant genetic model. Significant differences of the MMP-3 5A/6A polymorphism were also detected between FMMD patients and controls both in the dominant genetic model (OR = 0.23, 95% CI 0.08–0.68, p_corr = 0.048) and the additive genetic model (OR = 0.24, 95% CI 0.08–0.69, p_corr = 0.048). Conclusion: The functional polymorphism in the MMP-3 promoter might be associated with susceptibility to both MMD and FMMD in the Chinese Han population. The findings need to be validated in further studies including more subjects from different populations.

Moyamoya Disease in China

“…These findings support the view that a genetic factor may play a role in the incidence of MMD. [23][24] It is well-known that MMD occurs mostly in children in Asia. 13 However, the present study showed a preponderance of adults.…”

Twisted Blood Vessels: Symptoms, Etiology and Biomechanical Mechanisms

“…Tortuosity of cerebral arteries has been reported for aged, hypertensive patients [5,23,24,69] and in patients with ‘Moyamoya’ disease [70,71,72]. Cerebral arteries may also become tortuous due to malformation [73] or increased flow [34,35] associated with elastin degradation.…”

Importance of RNF213 polymorphism on clinical features and long-term outcome in moyamoya disease

“…though authors of recent genetic studies have made efforts to identify several candidate loci (chromosomes 3p24-26, 6q25, 8q23, 12p12, and 17q25 4,6,24,31 ) and several susceptibility genes (ACTA2, RPTOR, PDGFRB, MMP3, and TGFB1 2,3,15,16 ) related to MMD, the RING (Really Interesting New Gene) finger protein 213 gene (RNF213) is the only susceptibility gene for MMD identified by both genome-wide association studies and exome sequencing.…”