SNPs and Interaction Analyses of Noelin 2, Myocilin, and Optineurin Genes in Japanese Patients with Open-Angle Glaucoma

Abstract

The Arg144Gln mutation in OLFM2 is a possible disease-causing mutation in Japanese patients with OAG. Common polymorphisms in OLFM2 and OPTN may interactively contribute to the development of OAG, indicating a polygenic etiology.

Olfactomedin 2: Expression in the Eye and Interaction with Other Olfactomedin Domain–Containing Proteins

“…It is possible that these mutations in the OLFM2 gene interact with changes in other genes to produce an observable disease. This effect is exemplified by a recent analysis of gene-gene interaction using common SNPs by Funayama et al, 24 which indicated that OLFM2 and OPTN may interactively contribute to open-angle glaucoma.…”

“…Two reported OLFM2 mutants, T86M and R144Q, are associated with colorectal cancer 25 and glaucoma, respectively. 24 The disease with respect to mutations T86M and R144Q could be caused by altered cellular processes rather than accumulation of the protein due to reduced secretion. It is possible that these mutations in the OLFM2 gene interact with changes in other genes to produce an observable disease.…”

“…24 Both of these mutations are located outside the olfactomedin domain. It has been well demonstrated that glaucomacausing mutations in myocilin prevent or reduce its secretion and that more than 90% of such mutations are located in the olfactomedin domain.…”

“…23 Genetic data indicate that mutation of the OLFM2 gene in humans leading to the R144Q substitution in the protein sequence is a possible disease-causing mutation in Japanese patients with open-angle glaucoma. 24 The T86M substitution in the OLFM2 protein has been associated with colorectal cancers. 25 Overexpression of Olfm3 inhibits neurite outgrowth and induces Ca 2ϩ -dependent aggregation of NGFstimulated PC12 cells.…”

Molecular complexity of primary open angle glaucoma: current concepts

“…They observed two sets of interaction for HTG patients of OPTN IVS15+10G/A and OPTN IVS5+38T/G with MYOC Thr353Ile and APOE −491A/T respectively and three sets of interaction for NTG patients of OPTN Arg545Gln with APOE 2/ 3/ 4, MYOC -83G/A with APOE 2/ 3/ 4 and MYOC IVS2+35A/G and APOE −219T/G. Another interaction was also found between OPTN and OLFM2 in POAG pathogenesis (Funayama et al 2006). Incidentally, OLFM2 or olfactomedin2 was predicted to be a probable candidate gene of POAG by bioinformatics analysis from our lab (Mukhopadhyay et al 2004).…”