Phenotypic variability of cardiovascular manifestations in Marfan Syndrome. Possible role of hyperhomocysteinemia and C677T MTHFR gene polymorphism.
OBJECTIVE
The aim of this study was to evaluate (1) homocysteinemia and the prevalence of the C677T MTHFR polymorphism in Marfan patients and (2) whether the severity of cardiovascular manifestations is associated with homocysteinemia and/or C677T polymorphism.


RESULTS
We studied 107 patients subdivided into three subgroups based on the severity of cardiovascular manifestations: (A) no involvement (n=4); (B) mild involvement (n=45); (C) aortic dilatation or aortic dissection (n=58), and 189 controls. Total homocysteine (tHcy) was significantly higher in subgroup C than in subgroup B. In subgroup C patients with dissection tHcy was higher than in those without dissection. In subgroup C the prevalence of 677T homozygotes was higher, but not significantly, than in the subgroup B. In patients with dissection the prevalence of 677T homozygotes was significantly higher than in those without dissection and than in subgroup B. In the logistic regression analysis, severe cardiovascular manifestations and aortic dissection in Marfan patients were associated with tHcy plasma levels.


CONCLUSIONS
Our data indicate an association between the severity of the cardiovascular manifestations, in particular aortic dissection, and elevated tHcy levels. This suggests an important role for tHcy in determining phenotypic variability in Marfan patients and provides further evidence for the association of homocysteinemia with the damage of the vascular system.
Giusti
Betti
B
Dipartimento di Area Critica Medico Chirurgica, University of Florence, Florence, Italy. labtrombosi@ao-careggi.toscana.it
Porciani
Maria Cristina
MC
Brunelli
Tamara
T
Evangelisti
Lucia
L
Fedi
Sandra
S
Gensini
Gian Franco
GF
Abbate
Rosanna
R
Sani
Guido
G
Yacoub
Magdi
M
Pepe
Guglielmina
G
D000293:Adolescent; D000328:Adult; D000784:Aortic Dissection / Q000097:blood / Q000235:genetics; D001014:Aortic Aneurysm / Q000097:blood / Q000235:genetics; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics*; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index
D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2)