title: Association of Vitamin B12 Deficiency with Homozygosity of the TT MTHFR C677T Genotype, Hyperhomocysteinemia, and Endothelial Cell Dysfunction.
abstract: BACKGROUND
  Hyperhomocysteinemia is associated with increased cardiovascular risk, but treatment with folic acid has no effect on outcome in unselected patient populations.
  
  
  OBJECTIVE
  To confirm previous observations on the association of homozygosity for the TT MTHFR genotype with B12 deficiency and endothelial dysfunction, and to investigate whether patients with B12 deficiency should be tested for 677MTHFR genotype.
  
  
  METHODS
  We enrolled 100 individuals with B12 deficiency, tested them for the MTHFR C677T polymorphism and measured their homocysteine levels. Forearm endothelial function was checked in 23 B12-deficient individuals (13 with TT MTHFR genotype and 10 with CT or CC genotypes). Flow-mediated dilatation (FMD) was tested after short-term treatment with B12 and folic acid in 12 TT MTHFR homozygotes.
  
  
  RESULTS
  Frequency of the TT MTHFR genotype was 28/100 (28%), compared with 47/313 (15%) in a previously published cohort of individuals with normal B12 levels (P = 0.005). Mean homocysteine level was 21.2 ± 16 μM among TT homozygotes as compared to 12.3 ± 5.6 μM in individuals with the CC or CT genotype (P = 0.008). FMD was abnormal ( 6%) in 9/13 TT individuals with B12 deficiency (69%), and was still abnormal in 7/12 of those tested 6 weeks after B12 and folic treatment (58%).
  
  
  CONCLUSIONS
  Among individuals with B12 deficiency, the frequency of the TT MTHFR genotype was particularly high. The TT polymorphism was associated with endothelial dysfunction even after 6 weeks of treatment with B12 and folic acid. Based on our findings we suggest that B12 deficiency be tested for MTHFR polymorphism in order to identify potential vascular abnormalities and increased cardiovascular risk.
authors.forename: Avinoam
authors.initials: A
authors.lastname: Shiran
authors.forename: Eric
authors.initials: E
authors.lastname: Remer
authors.forename: Ihab
authors.initials: I
authors.lastname: Asmer
authors.forename: Basheer
authors.initials: B
authors.lastname: Karkabi
authors.forename: Eran
authors.initials: E
authors.lastname: Zittan
authors.forename: Aliza
authors.initials: A
authors.lastname: Cassel
authors.forename: Mira
authors.initials: M
authors.lastname: Barak
authors.forename: Orit
authors.initials: O
authors.lastname: Rozenberg
authors.forename: Khaled
authors.initials: K
authors.lastname: Karkabi
authors.forename: Moshe Y
authors.initials: MY
authors.lastname: Flugelman
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000627:therapeutic use; D006710:Homocysteine / Q000097:blood; D006720:Homozygote; D006801:Humans; D020138:Hyperhomocysteinemia / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D010807:Physical Endurance / Q000235:genetics; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D014805:Vitamin B 12 / Q000097:blood / Q000627:therapeutic use; D014806:Vitamin B 12 Deficiency / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D014815:Vitamins / Q000097:blood / Q000627:therapeutic use
chemical_list: D014815:Vitamins; D006710:Homocysteine; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12