title: Single Nucleotide Polymorphisms in the BDNF, VDR, and DNASE 1 Genes in Dry Eye Disease Patients: A Case-Control Study.
abstract: OBJECTIVE
  To identify single nucleotide polymorphisms (SNPs) in the brain-derived neurotrophic factor (BDNF), vitamin D receptor (VDR), and DNASE1 genes that may be associated with dry eye disease (DED), and determine whether this association varies by the presence of depression.
  
  
  METHODS
  A case-control study was performed with 64 DED cases and 51 controls. We collected 2 mL of saliva following a routine eye exam. Genotyping was performed using both custom and predesigned TaqMan SNP genotyping assays for 12 hypothesized SNPs. Genotype and allele frequencies of cases and controls were evaluated. Odds ratios were calculated for allele frequencies. Stratified analysis was performed to determine if the association between SNPs and DED varied by depression status.
  
  
  RESULTS
  A total of 18% of cases had the minor allele A of Val66Met (rs6265) SNP in the BDNF gene compared with 9% of the controls (P = 0.05). Odds ratio was 2.22. Two SNPs (Fokl-rs2228570 and Apal-rs7975232) in the VDR genes also varied between DED cases and controls. Cases were 1.72 and 1.66 times more likely to have the minor allele A in rs2228570 and rs7975232, respectively, than controls (P = 0.06 for both). While not statistically significant, among patients with depression, DED cases were 3.93 times more likely to have the minor allele A of the Val66Met SNP compared to controls.
  
  
  CONCLUSIONS
  This pilot study showed that Val66Met in the BDNF gene and two SNPs, Fokl and Apal, in the VDR gene may potentially be associated with DED. Additionally, the association between DED and Val66Met may vary by depression status.
authors.affiliation: Corneal Neurobiology Laboratory Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, College of Medicine, Chicago, Illinois, United States 2Quantitative Scientific Solutions, LLC, Arlington, Virginia, United States.
authors.forename: Joelle A
authors.initials: JA
authors.lastname: Hallak
authors.affiliation: Corneal Neurobiology Laboratory Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, College of Medicine, Chicago, Illinois, United States.
authors.forename: Sapna
authors.initials: S
authors.lastname: Tibrewal
authors.affiliation: Corneal Neurobiology Laboratory Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, College of Medicine, Chicago, Illinois, United States.
authors.forename: Neil
authors.initials: N
authors.lastname: Mohindra
authors.affiliation: Quantitative Ocular Genomics Laboratory, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, College of Medicine, Chicago, Illinois, United States.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Gao
authors.affiliation: Corneal Neurobiology Laboratory Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, College of Medicine, Chicago, Illinois, United States.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Jain
mesh_terms: D000483:Alleles; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D003850:Deoxyribonuclease I / Q000235:genetics* / Q000378:metabolism; D015352:Dry Eye Syndromes / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018167:Receptors, Calcitriol; C579455:BDNF protein, human; D004247:DNA; D003850:Deoxyribonuclease I