Transcobalamin 776C G polymorphism is associated with peripheral neuropathy in elderly individuals with high folate intake.
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.
The American journal of clinical nutrition