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A proteomic approach for the characterization of C677T mutation of the human gene methylenetetrahydrofolate reductase
Author(s) -
Greco Marilena,
Chiriacò Fernanda,
Del Boccio Piero,
Tagliaferro Luigi,
Acierno Raffaele,
Menegazzi Paola,
Pinca Eleonora,
Pignatelli Francesco,
Storelli Carlo,
Federici Giorgio,
Urbani Andrea,
Maffia Michele
Publication year - 2006
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200600130
Subject(s) - methylenetetrahydrofolate reductase , hyperhomocysteinemia , genotype , mutant , biology , apolipoprotein b , homocysteine , reductase , allele , genetics , mutation , gene , microbiology and biotechnology , biochemistry , enzyme , cholesterol
Methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of methylenetetrahydrofolate (CH 2 H 4 folate) to methyltetrahydrofolate (CH 3 H 4 folate). The C677T mutation is a common polymorphism of the human enzyme that leads to the replacement of Ala 222 Val, 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 p I 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.