BACKGROUND: Hyperhomocysteinemia is associated with increased cardiovascular risk, but treatment with folic acid has no effect on outcome in unselected patient populations. OBJECTIVES: 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.
BACKGROUND:Hyperhomocysteinemia is associated with increased cardiovascular risk, but treatment with folic acid has no effect on outcome in unselected patient populations. OBJECTIVES: 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 MTHFRC677T 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: Khalid M Al-Batayneh; Mazhar Salim Al Zoubi; Murad Shehab; Bahaa Al-Trad; Khaldon Bodoor; Wesam Al Khateeb; Alaa A A Aljabali; Mohammad Al Hamad; Greg Eaton Journal: J Med Biochem Date: 2018-04-01 Impact factor: 3.402
Authors: Bruce H R Wolffenbuttel; Hanneke J C M Wouters; M Rebecca Heiner-Fokkema; Melanie M van der Klauw Journal: Mayo Clin Proc Innov Qual Outcomes Date: 2019-05-27
Authors: Jéssica Vanessa de Carvalho Lisboa; Marina Ramalho Ribeiro; Rafaella Cristhine Pordeus Luna; Raquel Patrícia Ataíde Lima; Rayner Anderson Ferreira do Nascimento; Mussara Gomes Cavalcante Alves Monteiro; Keylha Querino de Farias Lima; Carla Patrícia Novaes Dos Santos Fechine; Naila Francis Paulo de Oliveira; Darlene Camati Persuhn; Robson Cavalcante Veras; Maria da Conceição Rodrigues Gonçalves; Flávia Emília Leite de Lima Ferreira; Roberto Teixeira Lima; Alexandre Sérgio da Silva; Alcides da Silva Diniz; Aléssio Tony Cavalcanti de Almeida; Ronei Marcos de Moraes; Eliseu Verly Junior; Maria José de Carvalho Costa Journal: Nutrients Date: 2020-01-30 Impact factor: 5.717
Authors: S Surendran; A Adaikalakoteswari; P Saravanan; I A Shatwaan; J A Lovegrove; K S Vimaleswaran Journal: Genes Nutr Date: 2018-02-06 Impact factor: 5.523