RT Journal Article
T1 WDR36 and P53 gene variants and susceptibility to primary open-angle glaucoma: Analysis of gene-gene interactions
A1 Blanco Marchite, C
A1 Sánchez Sánchez, F
A1 López, M. P.
A1 Iñigez, M
A1 López Martínez, F
A1 López Sánchez, E
A1 Alvarez, L
A1 Rodríguez, P. P
A1 Méndez Hernández, Carmen Dora
A1 Fernández Vega, L
A1 García Sánchez, Julián
A1 Coca Prados, M
A1 García Feijoo, Julián
A1 Escribano, J.
AB Purpose. To investigate the role of WDR36 and P53 sequence variations in POAG susceptibility. Methods. The authors performed a case-control genetic association study in 268 unrelated Spanish patients (POAG1) and 380 control subjects matched for sex, age, and ethnicity. WDR36 sequence variations were screened by either direct DNA sequencing or denaturing high-performance liquid chromatography. P53 polymorphisms p.R72P and c.97- 147ins16bp were analyzed by single-nucleotide polymorphism (SNP) genotyping and PCR, respectively. Positive SNP and haplotype associations were reanalyzed in a second sample of 211 patients and in combined cases (n = 479). Results. The authors identified almost 50 WDR36 sequence variations, of which approximately two-thirds were rare and one-third were polymorphisms. Approximately half the variants were novel. Eight patients (2.9%) carried rare mutations that were not identified in the control group (P = 0.001). Six Tag SNPs were expected to be structured in three common haplotypes. Haplotype H2 was consistently associated with the disease (P = 0.0024 in combined cases). According to a dominant model, genotypes containing allele P of the P53 p.R72P SNP slightly increased glaucoma risk. Glaucoma susceptibility associated with different WDR36 genotypes also increased significantly in combination with the P53 RP risk genotype, indicating the existence of a genetic interaction. For instance, the OR of the H2 diplotype estimated for POAG1 and combined cases rose approximately 1.6 times in the two-locus genotype H2/RP. Conclusions. Rare WDR36 variants and the P53 p.R72P polymorphism behaved as moderate glaucoma risk factors in Spanish patients. The authors provide evidence for a genetic interaction between WDR36 and P53 variants in POAG susceptibility, although this finding must be confirmed in other populations. © 2011 The Association for Research in Vision and
PB The Association for Research in Vision and Ophthalmology, Inc
YR 2011
FD 2011-10
LK https://hdl.handle.net/20.500.14352/107391
UL https://hdl.handle.net/20.500.14352/107391
LA eng
NO Blanco-Marchite C, Sánchez-Sánchez F, López-Garrido MP, Iñigez-de-Onzoño M, López-Martínez F, López-Sánchez E, Alvarez L, Rodríguez-Calvo PP, Méndez-Hernández C, Fernández-Vega L, García-Sánchez J, Coca-Prados M, García-Feijoo J, Escribano J. WDR36 and P53 gene variants and susceptibility to primary open-angle glaucoma: analysis of gene-gene interactions. Invest Ophthalmol Vis Sci. 2011 Oct 31;52(11):8467-78. doi: 10.1167/iovs.11-7489. PMID: 21931130; PMCID: PMC3208188.
NO Instituto de Salud Carlos III
NO Consejería de Sanidad (Castilla-La Mancha)
NO Ministerio de Insdutria y Turismo (España)
NO Fundación de Investigación Oftalmológica Fernández-Vega
NO Fundación Ma Cristina Masaveu Paterson
NO Fundación Rafael del Pino
NO Instituto Oftalmológico Fernández-Vega
DS Docta Complutense
RD 8 abr 2025