TY - JOUR
T1 - A proteomic approach for the characterization of C677T mutation of the human gene methylenetetrahydrofolate reductase
AU - Greco, Marilena
AU - Chiriacò, Fernanda
AU - Del Boccio, Piero
AU - Tagliaferro, Luigi
AU - Acierno, Raffaele
AU - Menegazzi, Paola
AU - Pinca, Eleonore
AU - Pignatelli, Francesco
AU - Storelli, Carlo
AU - Federici, Giorgio
AU - Urbani, Andrea
AU - Maffia, Michele
PY - 2006/10
Y1 - 2006/10
N2 - Methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of methylenetetrahydrofolate (CH2H4folate) to methyltetrahydrofolate (CH3H4folate). The C677T mutation is a common polymorphism of the human enzyme that leads to the replacement of Ala222Val, thermolability of MTHFR, and mild elevation of plasma homocysteine levels. A mild hyperhomocysteinemia is known to be risk factor for cardiovascular and thrombotic diseases, ischemic stroke, neural tube defects, late on-set dementia, and pregnancy complications. Human plasma of subjects carrying the C677T mutation in the MTHFR gene has been investigated for their protein pattern in order to identify novel molecular hallmarks. 2-D analysis of the plasma protein allowed the identification of a specific pattern associated with the TT mutant genotype. Noteworthy, we found one spot shifted to a more basic pI in mutant individuals, and MS identification corresponded to vitamin D-binding protein (DBP or group component (Gc) globulin). MS/MS peptide sequencing allowed to discriminate different allelic variants in the investigated clinical groups. These data confirmed by molecular genetic analysis highlight the novel association between the C677T MTHFR genotype with the Gc2 polymorphism of the DBP. Moreover, we found a quantitative reduction of Apolipoprotein A-I in mutant individuals, which was associated, in previous studies by others to an increased cardiovascular risk.
AB - Methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of methylenetetrahydrofolate (CH2H4folate) to methyltetrahydrofolate (CH3H4folate). The C677T mutation is a common polymorphism of the human enzyme that leads to the replacement of Ala222Val, thermolability of MTHFR, and mild elevation of plasma homocysteine levels. A mild hyperhomocysteinemia is known to be risk factor for cardiovascular and thrombotic diseases, ischemic stroke, neural tube defects, late on-set dementia, and pregnancy complications. Human plasma of subjects carrying the C677T mutation in the MTHFR gene has been investigated for their protein pattern in order to identify novel molecular hallmarks. 2-D analysis of the plasma protein allowed the identification of a specific pattern associated with the TT mutant genotype. Noteworthy, we found one spot shifted to a more basic pI in mutant individuals, and MS identification corresponded to vitamin D-binding protein (DBP or group component (Gc) globulin). MS/MS peptide sequencing allowed to discriminate different allelic variants in the investigated clinical groups. These data confirmed by molecular genetic analysis highlight the novel association between the C677T MTHFR genotype with the Gc2 polymorphism of the DBP. Moreover, we found a quantitative reduction of Apolipoprotein A-I in mutant individuals, which was associated, in previous studies by others to an increased cardiovascular risk.
KW - Apolipoprotein A-l
KW - Cardiovascular diseases
KW - Methylenetetrahydrofolate reductase
KW - Vitamin D-binding protein
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U2 - 10.1002/pmic.200600130
DO - 10.1002/pmic.200600130
M3 - Article
C2 - 16955529
AN - SCOPUS:33749611009
VL - 6
SP - 5350
EP - 5361
JO - Proteomics
JF - Proteomics
SN - 1615-9853
IS - 19
ER -