Transcobalamin 776C-->G polymorphism is associated with peripheral neuropathy in elderly with high folate intake

Authors: SAWAENGSRI, HATHAIRAT - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; BERGETHON, PETER - Pfizer, Inc; QIU, WENDY - Boston University; SCOTT, TAMMY - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; JACQUES, PAUL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; SELHUB, JACOB - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; PAUL, LIGI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/8/2016
Publication Date: 10/12/2016
Citation: Sawaengsri, H., Bergethon, P., Qiu, W.Q., Scott, T.M., Jacques, P.F., Selhub, J., Paul, L. 2016. Transcobalamin 776C-->G polymorphism is associated with peripheral neuropathy in elderly with high folate intake. American Journal of Clinical Nutrition. https://doi.org/10.3945/ajcn.116.139030.

Interpretive Summary: We investigated the relationship between a genetic variation in the protein transcobalamin, which transports vitamin B12 to cells, and peripheral neuropathy, or damage to the nervous system outside the brain and spinal cord, in the elderly. This variation may reduce the availability of vitamin B12 to tissues, even when vitamin B12 consumption is adequate. The results showed that individuals with the variant protein have 3-fold higher odds for peripheral neuropathy compared to those who lack the genetic variation. When total folate (a form of the B-vitamin) consumption from foods and supplements was taken into consideration, the odds for peripheral neuropathy were 7-fold higher for the individuals with the variation if they consumed more than twice the Recommended Dietary Allowance of folate (800 micrograms DFE/day) but not if they consumed less than this amount.

Technical 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 micrograms), 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 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.