title: Evaluation of a shorter methionine loading test.
abstract: We validated whether a shorter methionine loading test is as accurate as the original 6-h test in identifying hyperhomocysteinemic patients and investigated determinants of fasting and post-load homocysteine concentration. Plasma homocysteine was determined in EDTA-blood from women with a history of pre-eclampsia (n=106) after 12 h fasting and 3 and 6 h after an oral methionine load (0.1 g/kg body weight). The 677C>T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene, vitamin B6, vitamin B12, folate and creatinine were measured as determinants of homocysteine concentration. Good correlation and agreement between 3-h and 6-h plasma concentration of post-load (r=0.93, Kendall's tau-b=0.85) and delta (post-load minus the fasting value; r=0.90, Kendall's tau-b=0.79) homocysteine was observed and gross misclassification did not occur after division of 3-h and 6-h homocysteine scores into quartiles. Multiple linear regression revealed MTHFR 677 TT (p=0.01), folate (p=0.04) and vitamin B12 (p=0.06) as determinants of fasting homocysteine concentration; only MTHFR 677TT was related to 3-h (p=0.04) and 6-h (p=0.004) post-load homocysteine concentration. The MTHFR 677TT genotype resulted in >30% higher fasting and 3-h and 6-h post-load homocysteine concentrations compared to the wild-type CC genotype. This study shows that the 3-h methionine loading test is as good as the 6-h methionine loading test in identifying hyperhomocysteinemic patients. Furthermore, remethylation parameters (MTHFR 677C>T) strongly affect both fasting and post-load homocysteine.
authors.affiliation: Department of Clinical Chemistry, Erasmus MC, University Medical Center Rotterdam, 3000 CA, Rotterdam, The Netherlands. r.dejonge@erasmusmc.nl
authors.forename: Robert
authors.initials: R
authors.lastname: de Jonge
authors.forename: Pieter H
authors.initials: PH
authors.lastname: Griffioen
authors.forename: Bertrand
authors.initials: B
authors.lastname: van Zelst
authors.forename: R Montserrate
authors.initials: RM
authors.lastname: Brouns
authors.forename: Willy
authors.initials: W
authors.lastname: Visser
authors.forename: Jan
authors.initials: J
authors.lastname: Lindemans
mesh_terms: D000284:Administration, Oral; D000328:Adult; D002318:Cardiovascular Diseases / Q000209:etiology; D002614:Chelating Agents / Q000737:chemistry; D004492:Edetic Acid / Q000737:chemistry; D005215:Fasting; D005260:Female; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000175:diagnosis*; D016014:Linear Models; D008715:Methionine / Q000008:administration & dosage; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011225:Pre-Eclampsia; D011247:Pregnancy; D012307:Risk Factors; D013997:Time Factors
chemical_list: D002614:Chelating Agents; D006710:Homocysteine; D004492:Edetic Acid; D008715:Methionine; D042965:Methylenetetrahydrofolate Reductase (NADPH2)