Affiliations: Department of Pathology, University of Oklahoma Health
Sciences Center, Oklahoma City, OK, 73104, USA | University of Oklahoma Prevention Research Center,
University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104,
USA | Department of Medicine, University of Oklahoma Health
Sciences Center, Oklahoma City, OK 73104, USA | FreshGene, Inc., 200 Mason Circle, Suite C, Concord,
CA 94520, USA
Note: [] Corresponding author: Department of Pathology, University of
Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd., Oklahoma City, OK
73104, USA. Tel.: +1 405 2715249; Fax: +1 405 2713881; E-mail:
[email protected]
Abstract: Numerous studies have investigated the relationship between
polymorphisms, in particular 677C-T and 1298A-C, of the
methylene-tetrahydrofolate reductase (MTHFR) gene and coronary artery
disease (CAD) with conflicting results. This study investigates the potential
association of two point mutations in MTHFR, 677C-T and 1793G-A, along
with other risk factors, with CAD. This is the first hospital-based study to
investigate 1793G-A in this context. Genotype analysis was performed on 729
Caucasians and 66 African Americans undergoing coronary angiography using a
novel PCR-based assay involving formation of Holliday junctions. Allelic
frequencies for 677C-T were 66.2% C and 33.8% T for Caucasians and 90.9% C
and 9.1% T for African Americans. With respect to the 1793G-A polymorphism,
allelic frequencies were 94.7% G and 5.3% A for Caucasians and 99.2% G and
0.8% A for African Americans. Disease associations were examined in the
Caucasian patients due to their greater genotype variability and larger number
in the patient cohort. Results suggest that neither 677CT heterozygotes
(OR-1.36; 95% CI 0.95 to 1.96) nor mutant homozygotes (OR-0.73; 95% CI 0.44
to 1.20) have either an increased or decreased risk for CAD compared to the
677CC genotype. Likewise, the 1793GA genotype did not demonstrate a
statistically significant association with CAD compared to 1793GG patients
(OR-0.79; 95% CI 0.47 to 1.33). Mean homocysteine levels (μmol/L)
increased from normal to mutant for 677C-T (677CC: 10.2; 677CT: 11.0; 677TT:
11.6) and normal to heterozygous in 1793G-A (1793GG: 10.7; 1793GA: 11.5). These
MTHFR polymorphisms did not contribute to the prediction of clinically
defined CAD in Caucasians.
