Hyperhomocysteinemia: How Does it Affect the Development of Cardiovascular Disease?

Abstract

of the ones having atherosclerotic vascular disease, 13-47% show moderate to intermediate hyperhomocysteine levels [1,2].Changes in plasma homocysteine levels can result from the presence of several factors including physiological, genetic, nutritional, drug induced and hormonal factors. First studies indicating mild hyperhomocysteinemia as an independent risk factor for cardiovascular disease, with a prevalence of approximately 5% in the general population, date from the 80 th decade [3-6].

Associations of Serum Total Homocysteine Levels with Various Demographic, Clinical and Genetic Characteristics in Healthy Greek Adults

“…In our study, the individuals with 677TT genotype had significantly higher serum tHcy levels than individuals with the 677CC or 677CT genotypes, as other studies have also revealed (15)(16)(17). This finding could be attributed to thermolability induced in the enzyme MTHFR which results in its lower activity (approximately 70% for 677TT genotype) and therefore inability to efficiently convert 5,10-methylene-THF to 5-MTHF, a conversion necessary for the remethylation of Hcy to methionine (4)(5)(6)16). The significant contribution of the T allele on elevated serum tHcy levels and the statistically significant lower frequency of MTHFR 677CC genotype among individuals with serum tHcy levels ≥15 μmol/L than individuals with serum tHcy levels <15 μmol/L can justify the further investigation of HHcy individuals for a possible existence of MTHFR C677T polymorphism.…”

“…The function of the MTHFR enzyme is of great importance for the regulation of available 5-MTHF which is the predominant and biologically active form of circulating folate (1,7). Genetic defects in the enzymes or dietary deficiency of B-vitamin cofactors and their substrates could be responsible for elevations in the serum total Hcy (tHcy) levels (3)(4)(5)(6). Between the two well-known polymorphisms of the MTHFR gene, the C677T (substitution of C to T at the residue 677) and the A1298C (transversion of A to C at nucleotide position 1298), which affect the MTHFR enzymatic activity, only the first appears to be associated with increased serum tHcy levels (5).…”

“…It is known that a prolonged exposure to elevated serum tHcy levels, referred to as hyperhomocysteinemia (HHcy) (typically defined as serum tHcy levels ≥15 μmol/L)(4), is associated with a wide range of health problems and conditions including cardiovascular disease, deep vein thrombosis or pulmonary embolism, neurocognitive disorders, pregnancy complications (preeclampsia, placental abruption, pregnancy loss), birth defects, osteoporotic fractures, etc. (4)(5)(6)(8)(9)(10)(11). The aim of this study was to investigate the associations of serum tHcy levels with various demographic, genetic and clinical characteristics in healthy Greek adults.…”