title: Association of Toll-like receptor 4 single-nucleotide polymorphisms Asp299Gly and Thr399Ile with the risk of primary open angle glaucoma.
abstract: OBJECTIVE
  Toll-like receptor 4 (TLR4) is a transmembrane receptor that mediates immune responses to exogenous and endogenous ligands. Previously, non-coding single nucleotide polymorphisms (SNPs) in the TLR4 gene were related to primary open angle glaucoma (POAG). This study was undertaken to investigate whether coding TLR4 Asp299Gly (rs4986790 A/G) and Thr399Ile (rs4986791 C/T) are associated with POAG in a Mexican population.
  
  
  METHODS
  One hundred and eighty-seven unrelated Mexican patients with POAG (94 men and 95 women; mean age 66.49 ± 14.3 years) and 109 control subjects (40 men and 69 women; age, 63.28 ± 7.93 years) were included. SNPs Asp299Gly (rs4986790 A/G) and Thr399Ile (rs4986791 C/T) were genotyped by a Taqman® Allelic Discrimination Assayand. Allelic, genotypic, haplotypic, and model-based (dominant, recessive, and codominant) associations of the SNPs with POAG were analyzed using Chi-squared tests or Fisher exact tests and logistic regression.
  
  
  RESULTS
  Strong linkage disequilibrium was observed among the SNPs (D' = 0.8692), which were located in one haplotype block. With respect to allelic diversity, the minor allele of both SNPs generates a significantly increased risk of POAG. The minor allele of Asp299Gly conferred the highest increased risk of POAG (P = 0.0054, OR = 4.47, 95% CI = 1.46-13.70). With regard to genotypic diversity, individuals carrying the minor allele of Asp299Gly and Thr399Ile had a significant increased risk for POAG with OR of 4.47 (P = 0.054, 95% CI = 1.30-15.35) and 3.5, respectively (P = 0.012, 95% CI = 1.17-10.44). Haplotype analysis was non-significant.
  
  
  CONCLUSIONS
  TLR4 coding SNPs Asp299Gly and Thr399Ile might be used as genetic susceptibility alleles for POAG in Mexican population. Our findings support the role of TLR4 in the pathophysiology of glaucoma.
authors.affiliation: Tecnológico de Monterrey, División de Biotecnología y Salud, Campus Guadalajara, Guadalajara, Jalisco, México. josenavarro@itesm.mx.|Universidad Autónoma de Nayarit, Tepic, Nayarit, México. josenavarro@itesm.mx.|Edificio de Ciencias de la Salud, Tecnológico de Monterrey, Campus Guadalajara, Avenida General Ramón Corona, 2514, Zapopan, Jalisco, C.P. 45201, México. josenavarro@itesm.mx.
authors.forename: Jose
authors.initials: J
authors.lastname: Navarro-Partida
authors.affiliation: Universidad Autónoma de Nayarit, Tepic, Nayarit, México.
authors.forename: Abril Bernardette
authors.initials: AB
authors.lastname: Martinez-Rizo
authors.affiliation: Universidad Autónoma de Nayarit, Tepic, Nayarit, México.
authors.forename: Pedro
authors.initials: P
authors.lastname: Ramirez-Barrera
authors.affiliation: Universidad Autónoma de Nayarit, Tepic, Nayarit, México.
authors.forename: Jesus Bernardino
authors.initials: JB
authors.lastname: Velazquez-Fernandez
authors.affiliation: Universidad Autónoma de Nayarit, Tepic, Nayarit, México.
authors.forename: Veronica A
authors.initials: VA
authors.lastname: Mondragon-Jaimes
authors.affiliation: Tecnológico de Monterrey, División de Biotecnología y Salud, Campus Guadalajara, Guadalajara, Jalisco, México.
authors.forename: Arturo
authors.initials: A
authors.lastname: Santos-Garcia
authors.affiliation: Instituto Méxicano del Seguro Social, Delegación, Nayarit, México.
authors.forename: Veronica
authors.initials: V
authors.lastname: Benites-Godinez
mesh_terms: D000368:Aged; D000483:Alleles; D004247:DNA / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D004247:DNA
keywords: Asp299Gly; Polymorphisms; Primary open angle glaucoma; Thr399Ile; Toll-like receptor 4