title: Toward Novel Diagnostics for Primary Open-Angle Glaucoma? An Association Study of Polymorphic Variation in Ras Homolog Family Member (A, B, C, D) Genes RHOA, RHOB, RHOC, and RHOD.
abstract: The annual economic burden of visual disorders in the United States was estimated as $139 billion. The World Health Organization has listed glaucoma in the top 10 priority eye diseases. Primary open-angle glaucoma (POAG) is a common subtype, with a lack of clinical tools for early diagnosis. The Rho GTPases belong to the Ras superfamily of proteins; the RhoA immunostaining in the optic nerve head in human glaucoma is reportedly increased. We investigated the association of polymorphisms in the Ras Homolog Family Member A, B, C, and D genes (RHOA, RHOB, RHOC, and RHOD, respectively). In a total sample of 361 unrelated subjects (179 patients with POAG and 182 age- and sex-matched healthy controls), RHOA (rs6784820, rs974495), RHOB (rs62121967), RHOC (rs11102522), and RHOD (rs61891303, rs2282502) polymorphisms were characterized by the BioMark HD dynamic array system with real-time polymerarse chain reaction. Among these candidate genetic markers and considering the Bonferroni correction, RHOA rs974495 polymorphism was significantly associated with POAG (p = 0.0011), with the TT genotype increasing the disease risk 4.9 times (95% CI 1.630-15.023). The allele and haplotype distributions of the above RHO candidate polymorphisms did not diplay a significant association. This is the first study, to the best of our knowledge, to identify a significant genotypic association between POAG and RHOA gene rs974495 polymorphism. These observations warrant replication in independent samples in the pursuit of precision medicine for rapid and early glaucoma diagnosis, and molecular targets for innovation in therapeutics of this common eye disease.
authors.affiliation: 1 Department of Medical Pharmacology, Faculty of Medicine, Gaziantep University , Gaziantep, Turkey .
authors.forename: Ahmet
authors.initials: A
authors.lastname: Saracaloglu
authors.affiliation: 2 Department of Physiology, Faculty of Medicine, Gaziantep University , Gaziantep, Turkey .
authors.forename: Seniz
authors.initials: S
authors.lastname: Demiryürek
authors.affiliation: 3 Department of Ophthalmology, Faculty of Medicine, Gaziantep University , Gaziantep, Turkey .
authors.forename: Seydi
authors.initials: S
authors.lastname: Okumus
authors.affiliation: 4 Department of Medical Biology, Faculty of Medicine, Gaziantep University , Gaziantep, Turkey .
authors.forename: Serdar
authors.initials: S
authors.lastname: Oztuzcu
authors.affiliation: 4 Department of Medical Biology, Faculty of Medicine, Gaziantep University , Gaziantep, Turkey .
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Bozgeyik
authors.affiliation: 3 Department of Ophthalmology, Faculty of Medicine, Gaziantep University , Gaziantep, Turkey .
authors.forename: Erol
authors.initials: E
authors.lastname: Coskun
authors.affiliation: 3 Department of Ophthalmology, Faculty of Medicine, Gaziantep University , Gaziantep, Turkey .
authors.forename: Umit
authors.initials: U
authors.lastname: Aksoy
authors.affiliation: 3 Department of Ophthalmology, Faculty of Medicine, Gaziantep University , Gaziantep, Turkey .
authors.forename: Erdal
authors.initials: E
authors.lastname: Kaydu
authors.affiliation: 3 Department of Ophthalmology, Faculty of Medicine, Gaziantep University , Gaziantep, Turkey .
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Erbagci
authors.affiliation: 3 Department of Ophthalmology, Faculty of Medicine, Gaziantep University , Gaziantep, Turkey .
authors.forename: Bulent
authors.initials: B
authors.lastname: Gürler
authors.affiliation: 1 Department of Medical Pharmacology, Faculty of Medicine, Gaziantep University , Gaziantep, Turkey .
authors.forename: Belgin
authors.initials: B
authors.lastname: Alasehirli
authors.affiliation: 1 Department of Medical Pharmacology, Faculty of Medicine, Gaziantep University , Gaziantep, Turkey .
authors.forename: Abdullah T
authors.initials: AT
authors.lastname: Demiryürek
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000175:diagnosis / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D011110:Polymorphism, Genetic / Q000235:genetics*; D020741:rho GTP-Binding Proteins / Q000235:genetics; D020742:rhoA GTP-Binding Protein / Q000235:genetics*; D020743:rhoB GTP-Binding Protein / Q000235:genetics; D000075024:rhoC GTP-Binding Protein / Q000235:genetics
chemical_list: C066737:RHOA protein, human; C105243:RHOD protein, human; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D020743:rhoB GTP-Binding Protein; D000075024:rhoC GTP-Binding Protein