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Association Between a SLC23A2 Gene Variation, Plasma Vitamin C Levels, and Risk of Glaucoma in a Mediterranean Population

Vitamin C is water-soluble, and probably the most famous of all the vitamins. Even before its discovery in 1932, physicians recognised that there must be a compound in citrus fruits preventing scurvy, a disease that killed as many as 2 million sailors between 1500 and 1800. Later researchers discovered that man, other primates and the guinea pig depend on external sources to cover their Vitamin C requirements. Most other animals are able to synthesise Vitamin C from glucose and galactose in their body. The most prominent role of Vitamin C is its immune stimulating effect, which is important for the defence against infections such as common colds. It also acts as an inhibitor of histamine, a compound that is released during allergic reactions. As a powerful antioxidant it can neutralise harmful free radicals and aids in neutralising pollutants and toxins.

Zanon-Moreno V, Ciancotti-Olivares L, Asencio J, Sanz P, Ortega-Azorin C, Pinazo-Duran MD, Corella D. Association between a SLC23A2 gene variation, plasma Vitamin C levels, and risk of glaucoma in a Mediterranean population. 1. Mol Vis. 2011;17:2997-3004. Epub 2011 Nov 17.

PURPOSE: 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 ?g/ml versus 11.7?1.8 ?g/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 ?g/ml versus 10.5?1.6 ?g/ml, p<0.001 in POAG cases and 10.9?1.6 ?g/ml versus 12.1?1.8 ?g/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.