title: Transcobalamin 776C→G polymorphism is associated with peripheral neuropathy in elderly individuals with high folate intake.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA.
authors.forename: Hathairat
authors.initials: H
authors.lastname: Sawaengsri
authors.affiliation: Neuroscience and Pain Research Unit, Pfizer Inc., Cambridge, MA; and.
authors.forename: Peter R
authors.identifier: 0000-0001-9128-6574
authors.initials: PR
authors.lastname: Bergethon
authors.affiliation: Boston University School of Medicine, Boston, MA.
authors.forename: Wei Qiao
authors.initials: WQ
authors.lastname: Qiu
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA.
authors.forename: Tammy M
authors.initials: TM
authors.lastname: Scott
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Jacques
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Selhub
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA; ligi.paul_pottenplackel@tufts.edu.
authors.forename: Ligi
authors.identifier: 0000-0003-1909-4783
authors.initials: L
authors.lastname: Paul
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015992:Body Mass Index; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D004522:Educational Status; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000097:blood; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D010523:Peripheral Nervous System Diseases / Q000175:diagnosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D064167:Recommended Dietary Allowances; D014155:Transcobalamins / Q000235:genetics*; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000097:blood; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000097:blood
chemical_list: D014155:Transcobalamins; D014803:Vitamin B Complex; D005492:Folic Acid; D003404:Creatinine; D014805:Vitamin B 12
keywords: TCN2 776C>G polymorphism; folate; folic acid; peripheral neuropathy; transcobalamin; vitamin B-12