title: Association between a SLC23A2 gene variation, plasma vitamin C levels, and risk of glaucoma in a Mediterranean population.
abstract: OBJECTIVE
  Several dietary factors have been associated with glaucoma. Among them, dietary antioxidant intake (i.e., vitamin C and vitamin A) in association with glaucoma has been analyzed, but with mixed results. Genetic factors may play a role in modulating the effect of dietary antioxidant intake on glaucoma; however, nutrigenetic studies in this field are scarce. Our aim was to study the association between selected polymorphisms in key proteins related to vitamin C and vitamin A concentrations and primary open-angle glaucoma (POAG).
  
  
  METHODS
  We performed a case-control study matched for age, sex, and bodyweight. We recruited 300 subjects (150 POAG cases and 150 controls) from a Mediterranean population and determined the plasma concentrations of vitamin C and vitamin A for each subject. We selected the following single-nucleotide polymorphisms (SNPs) in genes related to vitamin A and vitamin C concentrations: rs176990 and rs190910 in the retinol-binding protein 1 (RBP1) gene; and rs10063949 and rs1279683 in the Na⁺-dependent L-ascorbic acid transporters 1 and 2, respectively (encoded by the SLC23A1 and SLC23A2 genes).
  
  
  RESULTS
  We found a statistically significant association between the rs1279386 (A>G) SNP in SLC23A2 and POAG risk. In the crude analysis, homozygous subjects for the G allele (GG subjects) had higher risk of POAG than other genotypes (OR: 1.67; 95% CI: 1.03-2.71). This association remained statistically significant (p=0.010) after multivariate adjustment for potential confounders. We also found that POAG patients had lower plasma vitamin C concentrations than control subjects (9.9±1.7 µg/ml versus 11.7±1.8 µg/ml, p<0.001). Moreover, we consistently detected a significant association between the rs1279386 SNP in SLC23A2 and plasma vitamin C concentrations: GG subjects had significantly lower plasma vitamin C concentrations than the other genotypes (9.0±1.4 µg/ml versus 10.5±1.6 µg/ml, p<0.001 in POAG cases and 10.9±1.6 µg/ml versus 12.1±1.8 µg/ml, p<0.001 in controls). The rs10063949 SNP in SLC23A1 was not associated with either plasma vitamin C concentrations or POAG risk. Similarly, SNPs in RBP1 were not associated with vitamin A concentrations or POAG risk.
  
  
  CONCLUSIONS
  The rs1279683 SNP in SLC23A2 was significantly associated with lower plasma concentrations of vitamin C and with higher risk of POAG in GG subjects.
authors.affiliation: Genetic & Molecular Epidemiology Unit, Department of Preventive Medicine & Public Health, School of Medicine, University of Valencia, Valencia, Spain. Vicente.Zanon-Moreno@uv.es
authors.forename: Vicente
authors.initials: V
authors.lastname: Zanon-Moreno
authors.forename: Lucia
authors.initials: L
authors.lastname: Ciancotti-Olivares
authors.forename: Jeronimo
authors.initials: J
authors.lastname: Asencio
authors.forename: Pedro
authors.initials: P
authors.lastname: Sanz
authors.forename: Carolina
authors.initials: C
authors.lastname: Ortega-Azorin
authors.forename: Maria D
authors.initials: MD
authors.lastname: Pinazo-Duran
authors.forename: Dolores
authors.initials: D
authors.lastname: Corella
mesh_terms: D000368:Aged; D001205:Ascorbic Acid / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D005902:Glaucoma, Open-Angle / Q000097:blood* / Q000235:genetics*; D006801:Humans; D008297:Male; D019083:Mediterranean Region; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D060347:Sodium-Coupled Vitamin C Transporters / Q000235:genetics*; D014801:Vitamin A / Q000097:blood
chemical_list: C555163:SLC23A2 protein, human; D060347:Sodium-Coupled Vitamin C Transporters; D014801:Vitamin A; D001205:Ascorbic Acid