The contribution of gene-gene interactions of polymorphic loci of matrix metalloproteinases to susceptibility to primary open-angle glaucoma in men
Background: Primary open-angle glaucoma (POAG) is a serious form of eye diseases leading to blindness and disability. Glaucoma in men occurs in more than half of cases (65%). The aim of the study: To study the contribution of gene-gene interactions of polymorphic loci of matrix metalloproteinases to susceptibility to primary open-angle glaucoma in men. Materials and methods: The study included 236 men with POAG (the diagnosis was confirmed by clinical, instrumental and laboratory examination methods) and 176 men of the control group without this disease. A molecular genetic study of 8 polymorphic loci of matrix metalloproteinase (MMP) genes was performed. The study of SNP×SNP interactions associated with the POAG development was conducted using the Arsampler program. Results: 16 models of SNP × SNP interactions of MMP genes (4 two-locus, 7 three-locus and 5 four-locus) that determine susceptibility to the development of POAG in men (pperm <0.05) were identified, among which 6 models are protective and 10 models are risk factors for the development of POAG (OR = 1.80-9.26). The models include all 8 MMP polymorphic loci studied: rs3918249, rs3787268, rs2250889, rs17577, rs17576, rs3918242 of the MMR-9 gene, rs1799750 of the MMP-1 gene, and rs679620 of the MMP-3 gene. Two polymorphisms (rs1799750 MMP-1 and rs2250889 MMP-9) are included in the largest number of models (10 and 8 models, respectively). The polymorphic rs1799750 and rs2250889 loci are of great functional importance in the body – they exhibit epigenetic effects associated with the expression level (cis-eQTL) of the MMP1, MMP10, WTAPP1, PLTP, PCIF1, NEURL2 genes and the level of alternative splicing of the SLC12A gene transcript, they determine the non-sync5 gene MMP-9 (p.Arg574Pro). Conclusion: Intergenic interactions of polymorphic MMP loci are associated with the POAG formation in men.
Svinareva DI. The contribution of gene-gene interactions of polymorphic loci of matrix metalloproteinases to susceptibility to primary open-angle glaucoma in men. Research Results in Biomedicine. 2020;6(1):63-77. (In Russian)
DOI: 10.18413/2658-6533-2020-6-1-0-6
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This work was financially supported by a grant from the President of the Russian Federation for leading scientific schools of the Russian Federation (project NSh-2609.2020.7).