Genotype-Phenotype Correlations in CYP1B1-Associated Primary Congenital Glaucoma Patients Representing Two Large Cohorts from India and Brazil

Genotype-Phenotype Correlations in CYP1B1-Associated Primary Congenital Glaucoma Patients Representing Two Large Cohorts from India and Brazil

Author Melo, Monica Barbosa de Google Scholar
Mandal, Anil K. Google Scholar
Tavares, Ivan Maynart Autor UNIFESP Google Scholar
Ali, Mohammed Hasnat Google Scholar
Kabra, Meha Google Scholar
Cabral de Vasconcellos, Jose Paulo Google Scholar
Senthil, Sirisha Google Scholar
Sallum, Juliana Maria Ferraz Autor UNIFESP Google Scholar
Kaur, Inderjeet Google Scholar
Betinjane, Alberto J. Google Scholar
Moura, Christiane Rolim de Autor UNIFESP Google Scholar
Paula, Jayter S. Google Scholar
Costa, Karita A. Autor UNIFESP Google Scholar
Sarfarazi, Mansoor Google Scholar
Della Paolera, Mauricio Google Scholar
Finzi, Simone Google Scholar
Ferraz, Victor E. F. Google Scholar
Costa, Vital P. Google Scholar
Belfort, Rubens Junior Autor UNIFESP Google Scholar
Chakrabarti, Subhabrata Google Scholar
Institution Universidade Estadual de Campinas (UNICAMP)
LV Prasad Eye Inst
Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Univ Connecticut
Irmandade Santa Casa de Misericordia São Paulo
Abstract BackgroundPrimary congenital glaucoma (PCG), occurs due to the developmental defects in the trabecular meshwork and anterior chamber angle in children. PCG exhibits genetic heterogeneity and the CYP1B1 gene has been widely implicated worldwide. Despite the diverse mutation spectra, the clinical implications of these mutations are yet unclear. the present study attempted to delineate the clinical profile of PCG in the background of CYP1B1 mutations from a large cohort of 901 subjects from India (n=601) and Brazil (n=300).MethodsGenotype-phenotype correlations was undertaken on clinically well characterized PCG cases from India (n=301) and Brazil (n=150) to assess the contributions of CYP1B1 mutation on a set of demographic and clinical parameters. the demographic (gender, and history of consanguinity) and quantitative clinical (presenting intraocular pressure [IOP] and corneal diameter [CD]) parameters were considered as binary and continuous variables, respectively, for PCG patients in the background of the overall mutation spectra and also with respect to the prevalent mutations in India (R368H) and Brazil (4340delG). All these variables were fitted in a multivariate logistic regression model using the Akaike Information Criterion (AIC) to estimate the adjusted odds ratio (OR) using the R software (version 2.14.1).ResultsThe overall mutation spectrum were similar across the Indian and Brazilian PCG cases, despite significantly higher number of homozygous mutations in the former (p=0.024) and compound heterozygous mutations in the later (p=0.012). A wide allelic heterogeneity was observed and only 6 mutations were infrequently shared between these two populations. the adjusted ORs for the binary (demographic) and continuous (clinical) variables did not indicate any susceptibility to the observed mutations (p>0.05).ConclusionsThe present study demonstrated a lack of genotype-phenotype correlation of the demographic and clinical traits to CYP1B1 mutations in PCG at presentation. However, the susceptibility of these mutations to the long-term progression of these traits are yet to be deciphered.
Language English
Sponsor Department of Science and Technology, Government of India
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number Department of Science and Technology, Government of India: DST/INT/BRAZIL/RPO-01/2008
CNPq: EU475687/20094
Date 2015-05-15
Published in Plos One. San Francisco: Public Library Science, v. 10, n. 5, 11 p., 2015.
ISSN 1932-6203 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent 11
Origin http://dx.doi.org/10.1371/journal.pone.0127147
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000354916100131
URI http://repositorio.unifesp.br/handle/11600/39106

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