title: Premature arterial and venous events in three families. Effect of folate levels and MTHFR mutation mediated by family/generation and homocysteine levels.
abstract: Plasma homocysteine levels result from the effect of genetic and environmental factors. We investigated the hypothesis of familial association between folates, methylenetetrahydrofolate reductase (MTHFR) and hyperhomocysteinemia with acute events, studying three families through pedigree analysis and log-linear graphical models. In 43 subjects, 13 had homocysteine levels of >15 micromol/l. In Family A, premature venous and arterial events occurred in father and son, respectively. In Family B, several arterial premature events occurred and very high homocysteine level was found in a healthy 18-year-old nephew. In Family C, stroke occurred at the age of 16 in a boy. In all three families, all subjects with premature cardiovascular events had high homocysteine level as well as MTHFR mutation, either homozygous or heterozygous. The present results underline that hyperhomocysteinemia has a direct conditional association with cardiovascular events. Moreover, homocysteine level is a variable that links the indirect association of folates, MTHFR mutation and cardiovascular event.
authors.affiliation: Cattedra di Cardiologia, Università di Brescia, Via Pisacane 4, 25123 Brescia, Italy. assanell@master.cci.unibs.it
authors.forename: Deodato
authors.initials: D
authors.lastname: Assanelli
authors.forename: M
authors.initials: M
authors.lastname: Grassi
authors.forename: A
authors.initials: A
authors.lastname: Bonanome
authors.forename: G
authors.initials: G
authors.lastname: Salvadori
authors.forename: P
authors.initials: P
authors.lastname: Bonetti
authors.forename: A
authors.initials: A
authors.lastname: Boldini
authors.forename: S
authors.initials: S
authors.lastname: Archetti
authors.forename: G
authors.initials: G
authors.lastname: Ruggeri
authors.forename: A
authors.initials: A
authors.lastname: Pezzini
authors.forename: A
authors.initials: A
authors.lastname: Pagnan
mesh_terms: D000293:Adolescent; D000328:Adult; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology* / Q000235:genetics; D005192:Family Health; D005260:Female; D005492:Folic Acid / Q000097:blood*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia; D007558:Italy / Q000453:epidemiology; D016014:Linear Models; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D009154:Mutation; D016017:Odds Ratio; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D010375:Pedigree
chemical_list: D006710:Homocysteine; D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)