Research Article: Meta-analysis of the rs243865 MMP-2 polymorphism and age-related macular degeneration risk

Date Published: March 7, 2019

Publisher: Public Library of Science

Author(s): Ricardo Usategui-Martín, Salvador Pastor-Idoate, Antonio J. Chamorro, Itziar Fernández, Iván Fernández-Bueno, Miguel Marcos-Martín, Rogelio González-Sarmiento, José Carlos Pastor, Demetrios G. Vavvas.


Several researchers have suggested that the rs243865 (16q13-q21) polymorphism in the promoter region of the metalloproteinase-2 (MMP-2) gene could be associated with an increased risk of developing age-related macular degeneration (AMD). However, previous results remain inconclusive. To clarify this controversy, we conducted a meta-analysis of the relationship between rs243865 of MMP-2 and AMD.

We included 6 independent case-control studies involving 1,682 AMD patients and 2,295 healthy subjects. The association between the rs243865 polymorphism and AMD was examined by the overall odds ratio (OR) with a 95% confidence interval (CI). We used a recessive genetic model analysis, sensitivity analysis, and assessment of bias in our meta-analysis.

Our results showed that there was no significant association between the variant T allele (p-value = 0.10, OR [95%CI] = 0.95 [0.82–1.10]) or the CT+TT genotype (p-value = 0.16, OR [95%CI] = 0.92 [0.76–1.12]) of rs243865 MMP-2 polymorphism and the presence of AMD.

The rs243865 MMP-2 polymorphism was not associated with an increased risk of developing AMD. The MMP-2 (-1306 C>T) promoter variant is unlikely to have a major role in AMD risk susceptibility.

Partial Text

Age-related macular degeneration (AMD) is the leading cause of severe vision loss and blindness worldwide, and the incidence in developed countries ranges from 9% to 25% at ages 65 to 75 years [1,2]. The risk of developing advanced AMD lesions increases with age and is ten-fold greater in people over 85 years compared those 65 to 75 years old [3]. According to the severity of the disease, AMD is classified as early, intermediate, and advanced. The advanced form includes atrophic and/or neovascular conditions [4].

The current study conformed to the checklist for meta-analysis of genetic association studies specified for PLOS One approach (S1 Table) [16].

The aetiology of AMD is unknown; nevertheless, several observations suggest that genetic alterations may be crucial in the development of the disease [5,6]. To date, through GWAS, more than 50 independently associated common genetic variants distributed across more than 30 loci have been associated with a significantly increased susceptibility to developing AMD [24–26]. To our knowledge, none of them included an analysis of the rs243865 MMP-2 polymorphism. In particular, variations in the complement factor H gene and the ARMS2/HTRA1 genes have been considered to be the most consistent genetic risk factors for AMD development [27,28]. The precise genetic factors, as well as their interactions, remain unclear in AMD. Therefore, in an attempt to prevent AMD, the identification of other potential genetic factors is crucial due to the lack of effective treatments at present.

In conclusion, our meta-analysis provides reliable evidence that rs243865 MMP-2 polymorphism is unlikely to be a risk factor for AMD development. Further investigations analysing the combined effect of genes and the environment may improve our current understanding of the association between the rs243865 or other MMP-2 polymorphisms and the risk of developing AMD, as well as the clinical and biological implications of other risk factors.




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