(Circulation. 1999;100:2406.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Methylenetetrahydrofolate Reductase Genotypes and Early-Onset Coronary Artery Disease
From the Departments of Cardiology (A.M., Y.B., Y.A.), Medicine D (S.L.), and Medical Genetics (T.S., N.M., M.S.), Rabin Medical Center, Beilinson Campus, Petah-Tiqva, and The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Correspondence to Aviv Mager, MD, Department of Cardiology, Rabin Medical Center, Beilinson Campus, Petah-Tiqva 49100, Israel.
Background—Homozygosity for the
common (677C
T) mutation in the
methylenetetrahydrofolate reductase
(MTHFR) gene is associated with hyperhomocysteinemia, but there is
uncertainty as to the association between this mutation and
coronary artery disease (CAD). This study examined the
association between MTHFR genotypes and age at onset of
CAD.
Methods and Results—Patients (n=169) with documented myocardial
infarction or angiographically documented CAD who were aged 
55 years
at onset of CAD symptoms and DNA samples from control subjects (n=313)
were studied. The prevalence of homozygosity among patients with early
CAD onset (aged 45 years) was 28%, which was significantly higher
than that in patients with later onset (13%) and in control subjects
(14%) (odds ratio 2.4, 95% CI 1.24 to 4.69, P=0.006,
and odds ratio 2.7, 95% CI 1.15 to 6.42, P=0.01,
respectively). Plasma folate was lower in TT homozygotes who had early
CAD onset than in those with later onset (P=0.005).
Among patients with plasma folate in the lowest quintile (12.6
nmol/L), 31% were homozygotes, as were 45% of those with low plasma
folate and early CAD onset. There was no difference in the prevalence
of traditional risk factors among genotypes. The frequency of
homozygosity in patients with 1 risk factor was higher than in those
with 
2 risk factors (30% versus 12%, P<0.05). In
multiple regression analysis, TT homozygosity and plasma folate
were independently associated with CAD, but the impact of folate was
small.
Conclusions—Homozygosity for the 677CT mutation of MTHFR is
common and is associated with an increased risk of premature CAD in
this population.
Key Words: genetics • coronary disease • risk factors • myocardial infarction
This article has been cited by other articles:
 |
|
 |
|
  C. Williams, B. A Kingwell, K. Burke, J. McPherson, and A. M Dart Folic acid supplementation for 3 wk reduces pulse pressure and large artery stiffness independent of MTHFR genotype Am. J. Clinical Nutrition, July 1, 2005; 82(1): 26 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. D. Spotila, P. F. Jacques, P. B. Berger, K. V. Ballman, R. C. Ellison, and R. Rozen Age Dependence of the Influence of Methylenetetrahydrofolate Reductase Genotype on Plasma Homocysteine Level Am. J. Epidemiol., November 1, 2003; 158(9): 871 - 877. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. L Ruberg and J. Loscalzo Prothrombotic determinants of coronary atherothrombosis Vascular Medicine, November 1, 2002; 7(4): 289 - 299. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Klerk, P. Verhoef, R. Clarke, H. J. Blom, F. J. Kok, E. G. Schouten, and and the MTHFR Studies Collaboration Group MTHFR 677C->T Polymorphism and Risk of Coronary Heart Disease: A Meta-analysis JAMA, October 23, 2002; 288(16): 2023 - 2031. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.D. Kark, R. Sinnreich, I.H. Rosenberg, P.F. Jacques, and J. Selhub Plasma Homocysteine and Parental Myocardial Infarction in Young Adults in Jerusalem Circulation, June 11, 2002; 105(23): 2725 - 2729. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Madonna, V. de Stefano, A. Coppola, F. Cirillo, A. M. Cerbone, G. Orefice, and G. Di Minno Hyperhomocysteinemia and Other Inherited Prothrombotic Conditions in Young Adults With a History of Ischemic Stroke Stroke, January 1, 2002; 33(1): 51 - 56. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Williams and P. F. Bray Genetics of Arterial Prothrombotic Risk States Experimental Biology and Medicine, May 1, 2001; 226(5): 409 - 419. [Abstract] [Full Text]
|
|
|
|
|
|
T. Kosokabe, K. Okumura, T. Sone, J. Kondo, H. Tsuboi, H. Mukawa, T. Tomida, T. Suzuki, H. Kamiya, H. Matsui, et al. Relation of a Common Methylenetetrahydrofolate Reductase Mutation and Plasma Homocysteine With Intimal Hyperplasia After Coronary Stenting Circulation, April 24, 2001; 103(16): 2048 - 2054. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Gallai, V. Caso, M. Paciaroni, G. Cardaioli, E. Arning, T. Bottiglieri, and L. Parnetti Mild Hyperhomocyst(e)inemia : A Possible Risk Factor for Cervical Artery Dissection Stroke, March 1, 2001; 32(3): 714 - 718. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. E Delvin, R. Rozen, A. Merouani, J. Genest Jr, and M. Lambert Influence of methylenetetrahydrofolate reductase genotype, age, vitamin B-12, and folate status on plasma homocysteine in children Am. J. Clinical Nutrition, December 1, 2000; 72(6): 1469 - 1473. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Chambers, H. Ireland, E. Thompson, P. Reilly, O. A. Obeid, H. Refsum, P. Ueland, D. A. Lane, and J. S. Kooner Methylenetetrahydrofolate Reductase 677 C->T Mutation and Coronary Heart Disease Risk in UK Indian Asians Arterioscler. Thromb. Vasc. Biol., November 1, 2000; 20(11): 2448 - 2452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Topol, J. McCarthy, S. Gabriel, D. J. Moliterno, W. J. Rogers, L. K. Newby, M. Freedman, J. Metivier, R. Cannata, C. J. O'Donnell, et al. Single Nucleotide Polymorphisms in Multiple Novel Thrombospondin Genes May Be Associated With Familial Premature Myocardial Infarction Circulation, November 27, 2001; 104(22): 2641 - 2644. [Abstract] [Full Text] [PDF]
|
|