title: WDR36 and P53 gene variants and susceptibility to primary open-angle glaucoma: analysis of gene-gene interactions.
abstract: OBJECTIVE
  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.
authors.affiliation: Servicio de Oftalmología, Complejo Hospitalario Universitario de Albacete (Hospital Perpetuo Socorro), Albacete, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Blanco-Marchite
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Sánchez
authors.forename: María-Pilar
authors.initials: MP
authors.lastname: López-Garrido
authors.forename: Mercedes
authors.initials: M
authors.lastname: Iñigez-de-Onzoño
authors.forename: Francisco
authors.initials: F
authors.lastname: López-Martínez
authors.forename: Enrique
authors.initials: E
authors.lastname: López-Sánchez
authors.forename: Lydia
authors.initials: L
authors.lastname: Alvarez
authors.forename: Pedro-Pablo
authors.initials: PP
authors.lastname: Rodríguez-Calvo
authors.forename: Carmen
authors.initials: C
authors.lastname: Méndez-Hernández
authors.forename: Luis
authors.initials: L
authors.lastname: Fernández-Vega
authors.forename: Julián
authors.initials: J
authors.lastname: García-Sánchez
authors.forename: Miguel
authors.initials: M
authors.lastname: Coca-Prados
authors.forename: Julián
authors.initials: J
authors.lastname: García-Feijoo
authors.forename: Julio
authors.initials: J
authors.lastname: Escribano
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D004843:Epistasis, Genetic / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D007429:Intraocular Pressure; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009798:Ocular Hypertension / Q000235:genetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D005136:Eye Proteins; D016159:Tumor Suppressor Protein p53; C502341:WDR36 protein, human