Ascorbate concentrations and polymorphisms in sodium transporter vitamin C genes in human plasma, aqueous humor and lens in an ascorbate depleted setting

Abstract

Purpose: We have previously reported low concentrations of plasma ascorbate and dietary vitamin C in the older Indian population and a strong inverse association of these measures with cataract. Little is known about ascorbate levels in human ocular tissues in populations habitually depleted of ascorbate or whether these are influenced by genetic polymorphisms.Our objectives were to investigate the relationship between plasma ascorbate and aqueous and lens ascorbate in India and whether these relationships are influenced by Single Nucleotide Polymorphisms (SNPs) in sodium vitamin C transporter genes (SLC23A1 and SLC23A2)

Methods: We measured ascorbate concentrations in plasma, aqueous and lens using high performance liquid chromatography in 60 patients undergoing cataract surgery in southern India. We genotyped four SNPs using TaqMan assay.

Results: The plasma ascorbate concentrations (µmol/L) were low: median and inter-quartile range (IQR), 15.2 (7.8, 34.5). Decreasing concentrations from the common to the rare genotype of aqueous ascorbate were observed for the SNPs rs6596473 (p <0.04) and for rs1247991 with lens ascorbate (p=0.02). The slope between log10 plasma ascorbate and aqueous ascorbate concentration, β = 1064, 95% CI= 814, 1315, p= 10-15, was modified by rs6596473 with a 2 fold difference between the common homozygous genotype (β= 1467) and the rare homozygous genotype (β= 641) and intermediate with the heterozygote (β= 1058), p interaction=0.03. The association of log10 plasma ascorbate was positively associated with lens ascorbate concentration p<0.003 but was not modified by rs6596473 p=0.6.

Conclusions: SNPs in sodium vitamin C transporter genes modify the relationships between plasma ascorbate and aqueous ascorbate.

Keywords: 445 cataract • 464 clinical (human) or epidemiologic studies: risk factor assessment • 618 nutritional factors