title: LOXL1 gene variants and their association with pseudoexfoliation glaucoma (XFG) in Spanish patients.
abstract: BACKGROUND
  LOXL1 gene is the most important genetic risk factor known so far for pseudoexfoliation glaucoma (XFG). Our purpose was to evaluate the potential association of individual genetic variants of the lysyl oxidase-like 1 (LOXL1) gene and haplotypes with XFG in Spanish patients.
  
  
  METHODS
  Blood samples were collected from a total of 105 Spanish patients with XFG and 200 healthy controls. The entire LOXL1 gene along with the promoter, coding and non-coding regions including the 5'- and 3'-untranslated regions, were sequenced using next-generation sequencing in 99 XFG patients. SNPs rs16958477 (promoter), rs1048661 (exon 1), rs3825942 (exon 1), rs2165241 (intron 1) and rs3522 (exon 7) in LOXL1 were genotyped by restriction fragment-length polymorphism (RFLP) in all Spanish control participants and in six additional XFG patients, and a case-control association study was performed. Comparisons of the allelic and genotypic frequencies were performed using standard χ(2) test with Bonferroni and Pearson corrections. Logistic regression analyses were permormed using Sigmaplot v11. Haplotypes frequencies were performed using HaploView 4.0.
  
  
  RESULTS
  Sequencing of the LOXL1 gene in XFG participants identified a total of 212 SNPs, of which 49 exhibited allelic frequencies with significant differences between cases and controls, and 66 were not previously described. The allele frequencies of SNPs rs16958477, rs1048661, rs3825942, rs2165241, were significantly associated with an increased risk for XFG, however the SNP rs3522 was not. The haplotype frequencies of SNPs rs16958477, rs1048661, rs3825942 and rs2165241 and their association with XFG indicated that the CGGT haplotype, containing all four risk alleles, and the AGGT haplotype, which carries the protective allele of rs16958477 and three risk alleles of the other three SNPs, were significantly associated with XFG (p = 4.5×10(-6), and p = 8.8×10(-6)), conferring more than 2-fold increased disease susceptibility.
  
  
  CONCLUSIONS
  SNPs of the LOXL1 gene are associated with XFG in the Spanish population. This information adds new support to the distinct risk association frequencies of LOXL1 alleles with XFG in Western European and Asian populations. Identification and validation of additional SNPs along the entire LOXL1 gene of XFG cases may provide insightful information on their potential role in the pathogenesis of this disease.
authors: Fundación de Investigación Oftalmológica, Instituto Oftalmológico Fernández-Vega, Avenida Doctores Fernández-Vega, 34, Oviedo, 33012, Spain. l.alvarez@fio.as.
authors: Lydia
authors: L
authors: Álvarez
authors: Fundación de Investigación Oftalmológica, Instituto Oftalmológico Fernández-Vega, Avenida Doctores Fernández-Vega, 34, Oviedo, 33012, Spain. mgarciadiaz@fio.as.
authors: Montserrat
authors: M
authors: García
authors: Fundación de Investigación Oftalmológica, Instituto Oftalmológico Fernández-Vega, Avenida Doctores Fernández-Vega, 34, Oviedo, 33012, Spain. h.gonzalez@fio.as.
authors: Héctor
authors: H
authors: González-Iglesias
authors: Laboratorio de Genética Molecular Humana, Facultad de Medicina/Instituto de Investigación en Discapacidades Neurológicas (IDINE), Universidad de Castilla-La Mancha, Albacete, 02006, Spain. julio.escribano@uclm.es.
authors: Julio
authors: J
authors: Escribano
authors: Fundación de Investigación Oftalmológica, Instituto Oftalmológico Fernández-Vega, Avenida Doctores Fernández-Vega, 34, Oviedo, 33012, Spain. pprcalvo@fernandez-vega.com.
authors: Pedro P
authors: PP
authors: Rodríguez-Calvo
authors: Fundación de Investigación Oftalmológica, Instituto Oftalmológico Fernández-Vega, Avenida Doctores Fernández-Vega, 34, Oviedo, 33012, Spain. prof.luis@fernandez-vega.com.
authors: Luis
authors: L
authors: Fernández-Vega
authors: Fundación de Investigación Oftalmológica, Instituto Oftalmológico Fernández-Vega, Avenida Doctores Fernández-Vega, 34, Oviedo, 33012, Spain. Miguel.Coca-Prados@yale.edu.|Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT, 06510, USA. Miguel.Coca-Prados@yale.edu.
authors: Miguel
authors: M
authors: Coca-Prados
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000235:genetics*; D001483:Base Sequence; D017889:Exfoliation Syndrome / Q000235:genetics*; D005787:Gene Frequency; D006801:Humans; D016015:Logistic Models; D008969:Molecular Sequence Data; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013030:Spain
chemical_list: D000594:Amino Acid Oxidoreductases; C445313:LOXL1 protein, human