An importance of identification of double variant methylenetetrahydrofolate reductase gene C677T and A1298C in cis configuration for pharmacogenetic studies

The Drop That Spilled the Cup: Acute Myocardial Infarction in a Young Woman with Underlying Thrombophilic Polymorphisms and Oral Contraceptive Use

“…The patient was also a carrier of MTHFR gene polymorphisms associated with CAD, peripheral artery disease (PAD), stroke, and neural tube defects [ 10 ].…”

Recurrent Venous Thrombosis: Is there a Place for Methylenetetrahydrofolate Reductase Polymorphisms?

“…However, Spiroski et al [7] found a statistically significant increase in homocysteine for the combined heterozygote haplotype [7]. An epidemiological study indicated that the combined effect of these two polymorphisms may be synergic mainly in the trans positions (mutation occurring in different alleles), therefore a combined polymorphisms and haplotype analysis may result in a more effective approach than a single polymorphism approach [8][9][10]. We did not investigate whether our patient presented MTHFR mutation in the cis or trans conformation, nor looked for linkage analysis, but regarding that our patient had increased levels of HCY, the presence of a trans form is more likely.…”

Characterization of a Rare Nonpathogenic Methylenetetrahydrofolatereductase (MTHFR) Gene Mutation p.Lys215del in a Southern Italian family

“…However, we identified this variant in a 66‐year‐old female referred to our laboratory for pharmacogenetic analysis before chemotherapy initiation following the resection of a moderately differentiated stage IIA adenocarcinoma of the sigma of 3.8 cm with largest diameter. Two common missense sequence variants of the MTHFR gene, the c.677C>T (p.Ala222Val; rs1801133) and the c.1298A>C (p.Glu429Ala; rs1801131), are indeed associated with a decreased enzymatic activity [Bottiger et al., ], thus having a pharmacogenetic role in predicting the efficacy and the toxicity of both fluoropyrimidines and antifolates, such as 5‐fluorouracil, raltitrexed, and methotrexate [De Mattia and Toffoli ; Palmirotta et al., ]. Molecular analysis of MTHFR c.677C>T and c.1298A>C (NG_013351.1) was performed in our patient as previously described [Palmirotta et al., ].…”

“…Two common missense sequence variants of the MTHFR gene, the c.677C>T (p.Ala222Val; rs1801133) and the c.1298A>C (p.Glu429Ala; rs1801131), are indeed associated with a decreased enzymatic activity [Bottiger et al., ], thus having a pharmacogenetic role in predicting the efficacy and the toxicity of both fluoropyrimidines and antifolates, such as 5‐fluorouracil, raltitrexed, and methotrexate [De Mattia and Toffoli ; Palmirotta et al., ]. Molecular analysis of MTHFR c.677C>T and c.1298A>C (NG_013351.1) was performed in our patient as previously described [Palmirotta et al., ]. Once the laboratory results are obtained, in order to perform a cosegregation study of this rare p.Lys215del mutation in the patient's family, we extended the molecular analyses to the proband's two sons.…”