Association of MTHFR C677T and A1298C Polymorphisms with Glaucoma Risk: a Systematic Review Meta-Analysis based 42 Case-Control Studies

Abstract

Aim: Several epidemiological studies have been performed to explore the association of MTHFR polymorphisms with glaucoma risk. However, the results were inconsistent or even inconclusive. Hence, we performed a meta-analysis to evaluate the association of MTHFR C677T and A1298C polymorphisms with glaucoma risk. Methods: A comprehensive literature search on PubMed, Google Scholar, EMBASE, and CNKI databases was performed to find all eligible studies up to January 30, 2019. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of such association. Results: A total of 42 case-control studies including 33 studies for MTHFR C677T and nine studies for A1298C polymorphism were selected. Pooled results showed that there was no significant association between the MTHFR C677T polymorphism and glaucoma risk. Similarly, no associations were found in subgroup analysis based on ethnicity and glaucoma type. However, there was a significant association between the A1298C polymorphism and the increased risk of glaucoma under heterozygote model (OR=0.765, 95% CI=0.626-0.935, P=0.009). Moreover, the significant association between MTHFR A1298C polymorphism and glaucoma were found by ethnicity and primary open angle glaucoma (POAG). Conclusions: The present meta-analysis revealed that MTHFR A1298C polymorphism is significantly associated with the increased risk of glaucoma, but not MTHFR C677T polymorphism.

Highlights on Genetic Polymorphism Associated with Thromboembolic Risk; Implications in Ophthalmic and Autoimmune Disorders—A Review

“…There are studies implying that genetic polymorphism, such as variant MTHFR A1298C, may increase the risk for developing glaucoma, especially in the heterozygote model [ 9 , 22 ]. However, in order to support this idea, extended studies are still necessary [ 7 ].…”

“…Primary glaucoma is classified in primary open angle glaucoma (POAG), primary congenital glaucoma (PCG) and primary angle-closure glaucoma (PACG). There are several studies that support that genetic polymorphism, such as the variant MTHFR A1298C, may increase the risk for developing glaucoma, especially in the heterozygote model [ 9 , 22 ]. However, while there are meta-analyses supporting this idea, other studies are yet to be extended, given the fact that, while some of these studies tried to maintain a heterogeneity of the assessed patients, other studies were made on specific ethnic groups [ 7 ].…”

“…The main cause involved in this outcome may be the result of an accelerated atherosclerotic process. Both RA and atherosclerosis are complex polygenic diseases, and both are chronic inflammatory diseases with similar pathophysiological mechanisms [ 22 ], which display a strong genetic component of susceptibility. RA has an estimated heritability of up to 60% and cardiovascular disease in the general population of up to 30%–60%.…”

Association of MTHFR C677T polymorphism with primary open angle glaucoma: a Meta-analysis based on 18 case-control studies

“…We found some problems when reviewing previous literatures. For example, Gohari et al [33] , based on 33 studies with 3504 glaucoma patients and 2525 controls, offered different opinion on the MTHFR C677T susceptibility with glaucoma (containing POAG patients). We found they might miscalculate the frequency of TC genotype and misclassified the source of control from hospital-based group into the community-based ones [15] .…”

Homocysteine and Glaucoma

“…Because photoreceptors initiate visual transduction, their absence could result in the death of RGCs due to the lack of stimulation earlier in the pathway. Moreover, because homocysteine metabolism occurs in every cell, its defective metabolism within both the RGCs and optic nerve can be another possibility behind the mechanism of HHcy-associated POAG [ 127 , 128 ]. In fact, a functional analysis of the mthfr mutant mice demonstrated that HHcy in the retina of mice led to increased RGC death [ 129 ].…”