Abstract
Mild hyperhomocysteinemia is considered an important risk factor for vascular disease. A common polymorphism (677C → T) in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with a decreased enzyme activity and consequent higher circulating levels of homocysteine. We hypothesized that the serum levels of homocysteine and/or the MTHFR polymorphism could influence the risk for coronary artery disease (CAD) in patients with heterozygous familial hypercholesterolemia (FH), who are genetically prone to atherosclerosis. We determined the MTHFR genotype and fasting total serum homocysteine level in 249 adult patients (103 males and 146 females) with heterozygous FH. MTHFR polymorphism was a major determinant of serum homocysteine in adult FH of both sexes. The logistic regression analysis showed that in FH patients a high level of homocysteine (>12 μmol/l, corresponding to the upper quartile of serum distribution) was the most significant predictor of CAD (n = 99) in all the groups considered (all CAD, previous myocardial infarction, myocardial infarction plus angiographically confirmed CAD). The adjusted odds ratio (OR (95% CI)) for the homocysteine-associated risk of CAD (upper quartile versus lower quartiles) was 3.27 (1.60-6.62) in males and females considered together, 5.67 (1.50-21.3) in males and 2.78 (1.17-6.62) in females. LDL cholesterol (upper quartile versus lower quartiles) and hypertension were the other variables independently associated with CAD. In both sexes MTHFR polymorphism was not an independent predictor of CAD. Plasma concentration of serum homocysteine, but not MTHFR genotype, is associated with an increased risk of CAD in male and female patients with heterozygous FH.
| Original language | English |
|---|---|
| Pages (from-to) | 333-338 |
| Number of pages | 6 |
| Journal | Atherosclerosis |
| Volume | 179 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Apr 2005 |
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Keywords
- Coronary artery disease
- Familial hypercholesterolemia
- Homocysteine
- Methylenetetrahydrofolate reductase
- Myocardial infarction
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
Serum homocysteine, methylenetetrahydrofolate reductase gene polymorphism and cardiovascular disease in heterozygous familial hypercholesterolemia. / Pisciotta, Livia; Cortese, Claudio; Gnasso, Agostino; Liberatoscioli, Laura; Pastore, Anna; Mannucci, Liliana; Irace, Concetta; Federici, Giorgio; Bertolini, Stefano.
In: Atherosclerosis, Vol. 179, No. 2, 04.2005, p. 333-338.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Serum homocysteine, methylenetetrahydrofolate reductase gene polymorphism and cardiovascular disease in heterozygous familial hypercholesterolemia
AU - Pisciotta, Livia
AU - Cortese, Claudio
AU - Gnasso, Agostino
AU - Liberatoscioli, Laura
AU - Pastore, Anna
AU - Mannucci, Liliana
AU - Irace, Concetta
AU - Federici, Giorgio
AU - Bertolini, Stefano
PY - 2005/4
Y1 - 2005/4
N2 - Mild hyperhomocysteinemia is considered an important risk factor for vascular disease. A common polymorphism (677C → T) in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with a decreased enzyme activity and consequent higher circulating levels of homocysteine. We hypothesized that the serum levels of homocysteine and/or the MTHFR polymorphism could influence the risk for coronary artery disease (CAD) in patients with heterozygous familial hypercholesterolemia (FH), who are genetically prone to atherosclerosis. We determined the MTHFR genotype and fasting total serum homocysteine level in 249 adult patients (103 males and 146 females) with heterozygous FH. MTHFR polymorphism was a major determinant of serum homocysteine in adult FH of both sexes. The logistic regression analysis showed that in FH patients a high level of homocysteine (>12 μmol/l, corresponding to the upper quartile of serum distribution) was the most significant predictor of CAD (n = 99) in all the groups considered (all CAD, previous myocardial infarction, myocardial infarction plus angiographically confirmed CAD). The adjusted odds ratio (OR (95% CI)) for the homocysteine-associated risk of CAD (upper quartile versus lower quartiles) was 3.27 (1.60-6.62) in males and females considered together, 5.67 (1.50-21.3) in males and 2.78 (1.17-6.62) in females. LDL cholesterol (upper quartile versus lower quartiles) and hypertension were the other variables independently associated with CAD. In both sexes MTHFR polymorphism was not an independent predictor of CAD. Plasma concentration of serum homocysteine, but not MTHFR genotype, is associated with an increased risk of CAD in male and female patients with heterozygous FH.
AB - Mild hyperhomocysteinemia is considered an important risk factor for vascular disease. A common polymorphism (677C → T) in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with a decreased enzyme activity and consequent higher circulating levels of homocysteine. We hypothesized that the serum levels of homocysteine and/or the MTHFR polymorphism could influence the risk for coronary artery disease (CAD) in patients with heterozygous familial hypercholesterolemia (FH), who are genetically prone to atherosclerosis. We determined the MTHFR genotype and fasting total serum homocysteine level in 249 adult patients (103 males and 146 females) with heterozygous FH. MTHFR polymorphism was a major determinant of serum homocysteine in adult FH of both sexes. The logistic regression analysis showed that in FH patients a high level of homocysteine (>12 μmol/l, corresponding to the upper quartile of serum distribution) was the most significant predictor of CAD (n = 99) in all the groups considered (all CAD, previous myocardial infarction, myocardial infarction plus angiographically confirmed CAD). The adjusted odds ratio (OR (95% CI)) for the homocysteine-associated risk of CAD (upper quartile versus lower quartiles) was 3.27 (1.60-6.62) in males and females considered together, 5.67 (1.50-21.3) in males and 2.78 (1.17-6.62) in females. LDL cholesterol (upper quartile versus lower quartiles) and hypertension were the other variables independently associated with CAD. In both sexes MTHFR polymorphism was not an independent predictor of CAD. Plasma concentration of serum homocysteine, but not MTHFR genotype, is associated with an increased risk of CAD in male and female patients with heterozygous FH.
KW - Coronary artery disease
KW - Familial hypercholesterolemia
KW - Homocysteine
KW - Methylenetetrahydrofolate reductase
KW - Myocardial infarction
UR - http://www.scopus.com/inward/record.url?scp=14944385144&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=14944385144&partnerID=8YFLogxK
U2 - 10.1016/j.atherosclerosis.2004.10.016
DO - 10.1016/j.atherosclerosis.2004.10.016
M3 - Article
VL - 179
SP - 333
EP - 338
JO - Atherosclerosis
JF - Atherosclerosis
SN - 0021-9150
IS - 2
ER -