Transcobalamin 776C/G polymorphism is associated with peripheral neuropathy in elderly individuals with high folate intake1-3

Abstract

Background: The 776C/G polymorphism of the Vitamin B-12 transport protein transcobalamin gene (TCN2) (rs1801198; Pro259Arg) is associated with a lower holotranscobalamin concentration in plasma. This effect may reduce the availability of Vitamin B-12 to tissues even when Vitamin B-12 intake is adequate. Clinical outcomes associated with Vitamin B-12 insufficiency could potentially be worsened by high folate intake. Objective: We determined the association of the TCN2 776C/G polymorphism and folate intake with peripheral neuropathy in elders with normal plasma concentrations of Vitamin B-12. Design: Participants in this cross-sectional study (n = 171) were from a cohort of community-based, home-bound elderly individuals aged 60 y who underwent an evaluation by physicians including an assessment for peripheral neuropathy. Participants were administered food-frequency and general health status questionnaires, anthropometric measurements were taken, and a fasting blood sample from each subject was collected. Results: Odds of neuropathy were 3-fold higher for GG genotypes than for CC genotypes (OR: 3.33; 95% CI: 1.15, 9.64). When folate intake was .2 times the Recommended Dietary Allowance (800 mg), GG genotypes had 6.9-fold higher odds of neuropathy than CC genotypes (OR: 6.9; 95% CI: 1.31, 36.36). There was no difference between the genotypes in the odds of peripheral neuropathy when folate intake was #800 mg (OR: 1.5; 95% CI: 0.18, 12.33). Conclusion: The TCN2 776C/G polymorphism is associated with increased odds of peripheral neuropathy in the elderly, even with a normal Vitamin B-12 status, especially if their folate intake is .2 times the Recommended Dietary Allowance.