title: Association of single-nucleotide polymorphisms in non-coding regions of the TLR4 gene with primary open angle glaucoma in a Mexican population.
abstract: Toll-like receptor 4 (TLR4) non-coding polymorphisms are associated to primary open angle glaucoma (POAG), normal tension glaucoma, and pseudoexfoliation glaucoma. This study was performed to determine whether non-coding single nucleotide polymorphisms (SNPs) in the TLR4 gene contribute to POAG in a Mexican population.
  
  
  
  A total of 187 unrelated Mexican patients with POAG and 109 control subjects were included. Allelic, genotypic, and haplotypic diversity was assessed for the non-coding polymorphisms rs11536889, rs1927911, rs12377632, and rs2149356 of the TLR4 gene. Genotyping of target SNPs was performed by 5' exonuclease allelic discrimination assays.
  
  
  
  Strong linkage disequilibrium was observed among the SNPs (D' > 0.818), which were located in one haplotype block. The rs11536889 polymorphism was not associated to POAG in any case. The frequency of the minor allele of rs2149356 was significantly higher in the glaucoma group, conferring an increased risk of POAG (p = 0.0018, OR = 1.803, 95% CI 1.2556-2.5890) whereas minor allele of rs12377632 was significantly lower, attributing a protective effect (p = 0.0001, OR = 0.6662, 95% CI 0.4753-0.9339). Subjects with genotypes carrying the minor allele of rs1927911 and rs2149356 shown an increased risk for POAG (p = 0.03, OR = 1.78, 95% CI 1.10-2.87, and p < 0.0004, OR =2.62, 95%CI 1.61-4.27 respectively). Finally, we found significant risk haplotypes. The GTT haplotype (constituted by rs1927911, rs12377632, and rs2149356) reached the higher OR (p = 0.0026, OR = 4.70, 95% CI 1.73-12.77).
  
  
  
  We have identified intronic TLR4 SNPs as genetic susceptibility alleles for POAG in a Mexican population. Our findings support the association of the TLR4 gene with POAG.
authors.affiliation: a División de Biotecnología y Salud, Campus Guadalajara , Tecnológico de Monterrey , Guadalajara , Jalisco , México.
authors.forename: Jose
authors.initials: J
authors.lastname: Navarro-Partida
authors.affiliation: b Instituto Mexicano del Seguro Social , Centro Médico Nacional de Occidente , Guadalajara , Jalisco , México.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Alvarado Castillo
authors.affiliation: c Unidad Académica de Medicina , Universidad Autónoma de Nayarit , Tepic , Nayarit , México.
authors.forename: Abril Bernardette
authors.initials: AB
authors.lastname: Martinez-Rizo
authors.affiliation: c Unidad Académica de Medicina , Universidad Autónoma de Nayarit , Tepic , Nayarit , México.
authors.forename: Ramses
authors.initials: R
authors.lastname: Rosales-Diaz
authors.affiliation: d Secretaría de Investigación y Posgrado , Universidad Autónoma de Nayarit , Tepic , Nayarit , México.
authors.forename: Jesus Bernardino
authors.initials: JB
authors.lastname: Velazquez-Fernandez
authors.affiliation: a División de Biotecnología y Salud, Campus Guadalajara , Tecnológico de Monterrey , Guadalajara , Jalisco , México.
authors.forename: Arturo
authors.initials: A
authors.lastname: Santos
mesh_terms: D000368:Aged; D000483:Alleles; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D060005:Genotyping Techniques; D005902:Glaucoma, Open-Angle / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008800:Mexico / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D022661:RNA, Untranslated / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: D022661:RNA, Untranslated; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4
keywords: Non-coding regions; polymorphisms; primary open angle glaucoma; toll-like receptor 4