Transcobalamin 776C→G polymorphism is associated with peripheral neuropathy in elderly individuals with high folate intake

Am J Clin Nutr. 2016 Dec;104(6):1665-1670. doi: 10.3945/ajcn.116.139030. Epub 2016 Oct 12.


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 μg), 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 μg (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.

Keywords: TCN2 776C>G polymorphism; folate; folic acid; peripheral neuropathy; transcobalamin; vitamin B-12.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Body Mass Index
  • Creatinine / blood
  • Cross-Sectional Studies
  • Educational Status
  • Female
  • Folic Acid / administration & dosage*
  • Folic Acid / blood
  • Genotype
  • Humans
  • Logistic Models
  • Male
  • Peripheral Nervous System Diseases / diagnosis
  • Peripheral Nervous System Diseases / genetics*
  • Polymorphism, Single Nucleotide*
  • Recommended Dietary Allowances
  • Transcobalamins / genetics*
  • Vitamin B 12 / administration & dosage
  • Vitamin B 12 / blood
  • Vitamin B Complex / administration & dosage
  • Vitamin B Complex / blood


  • Transcobalamins
  • Vitamin B Complex
  • Folic Acid
  • Creatinine
  • Vitamin B 12