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| Author(s): |
Hugo Freire Nunes
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia |
| Defense date: | 2016-08-29 |
| Examining board members: |
Mônica Barbosa de Melo;
Edi Lúcia Sartorato;
Edmilson Ricardo Gonçalves;
Sueli Matilde da Silva Costa;
Niro Kasahara
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| Advisor: | Nilson Ivo Tonin Zanchin; Mônica Barbosa de Melo |
| Abstract | |
Glaucoma is one the leading causes of irreversible blindness worldwide and primary open angle glaucoma (POAG) is the most common form of the disease. This affection is difficult to be detected once it is asymptomatic at early stages, when treatment could prevent definitive vision loss. Hence, the identification of risk groups based on genetic aspects is important to help in early diagnosis and to provide a clinical segment more adequate to the patients. Genes related to POAG have been identified, including MYOC, OPTN and WDR36. Mutations in the MYOC gene are considered one of the few causes of blindness with established molecular basis. More recently, the NTF4 gene has been identified through linkage studies in the German population; CAV1 and CDKN2B have been associated to POAG by means of Genome Wide Association Studies (GWAS) and replicated in other populations. The possible implications of some of these genes in the physiopathology of POAG remains unrecognized and there is no data about their participation in the Brazilian population. Besides that only few genes have known influence in POAG physiopathology, stimulating the search for new genes. This study proposed, initially, to investigate the association of the NTF4 gene with glaucoma by means of the analysis of its coding region in a case-control study in a cohort comprised by affected versus unaffected unrelated individuals. Additionally, the contribution of risk alleles previously associated with POAG in the regions of CAV1 (rs4236601) and CDKN2B (rs4977756 and rs2157719) genes was investigated. Concomitantly, thirteen families were analyzed by means of the investigation of the coding region of MYOC and CYP1B1 genes. In two families without mutations in the MYOC gene, exome sequencing was performed aiming to discover new causal variants to POAG. Mutations in the NTF4 gene are not common and in our analysis no mutation was found in this gene that could be related to the disease in this Brazilian sample. However, in order to confirm these results, regulatory regions of the gene have to be evaluated. Our results showed that recently described genetic markers next to CAV1/2 (rs4236601, p=0,04) and CDKN2B (rs2157719 p=0.0005) were associated with POAG in the studied sample, results that are being described for the first time in Brazil. Family studies describe few genes that cause the mendelian forms of POAG. Our study hasn¿t found mutations in the MYOC gene in thirteen adult onset POAG families, which was expected once mutations in this gene are more common in the juvenile form of the disease. Seven mutations in the CYP1B1 gene were described in the same families, however only one mutation, P400S, may be related with glaucoma. In order to elucidate the relation of this variant with POAG the follow-up of carrier individuals is required. We performed exome sequencing in two families with POAG but yet no mutations have been found that segregate with the disease in ten individuals evaluated (AU) | |
| FAPESP's process: | 11/04073-7 - Genetics aspects of primary open-angle glaucoma(POAG)in the brazilian population |
| Grantee: | Hugo Freire Nunes |
| Support Opportunities: | Scholarships in Brazil - Doctorate |