title: The graded effect of hyperhomocysteinemia on the severity and extent of coronary atherosclerosis.
abstract: It is not clear to what extent methylenetetrahydrofolate reductase (MTHFR) gene and hyperhomocysteinemia effect the severity and extent of coronary atherosclerosis in Asian populations. We examined the MTHFR genotypes and plasma homocysteine (HCY) concentrations in 192 Taiwanese and investigated their relationship with coronary artery disease (CAD), and the severity and extent of coronary atherosclerosis. The distribution of MTHFR genotypes was similar in 116 CAD patients and 76 non-CAD subjects. Homozygosity was noted in 8% of CAD patients and 13% of non-CAD subjects (P=0.33; 95% CI, 0. 2-1.6). The geometric mean of HCY values was higher in CAD patients (11.10+/-1.51 micromol/l) than in non-CAD subjects (9.21+/-1.55 micromol/l) (P=0.003). HCY levels were higher in patients with multi-vessel disease (P<0.05) or in patients with > or = 90% stenotic lesions (P=0.005), compared with non-CAD subjects. The CAD risks in the top two HCY quartiles (> or = 14.0 and 10.1-13.9 micromol/l) were 4.0 (95% CI, 1.7-9.2) and 3.2 (95% CI, 1.4-7.4) times higher than in the lowest quartile (< or = 7.9 micromol/l) (P=0.001 and 0.007, respectively). Linear regression analysis showed significant correlations between HCY concentrations and the severity and extent of atherosclerosis (P=0.0001 for both). In conclusion, hyperhomocysteinemia appears to have a graded effect on the risk of CAD as well as the severity and extent of coronary atherosclerosis. Our findings do not support the homozygous genotype of MTHFR as a genetic risk factor for CAD in this Taiwanese population. Perhaps a further study including assessment of vitamin status is needed to better clarify the relationship between MTHFR genotypes and CAD.
authors.affiliation: Department of Internal Medicine (Cardiology), National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan, ROC.
authors.forename: C L
authors.initials: CL
authors.lastname: Chao
authors.forename: H H
authors.initials: HH
authors.lastname: Tsai
authors.forename: C M
authors.initials: CM
authors.lastname: Lee
authors.forename: S M
authors.initials: SM
authors.lastname: Hsu
authors.forename: J T
authors.initials: JT
authors.lastname: Kao
authors.forename: K L
authors.initials: KL
authors.lastname: Chien
authors.forename: F C
authors.initials: FC
authors.lastname: Sung
authors.forename: Y T
authors.initials: YT
authors.lastname: Lee
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001483:Base Sequence; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000453:epidemiology* / Q000209:etiology* / Q000503:physiopathology; D005260:Female; D006306:Health Surveys; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics; D016133:Polymerase Chain Reaction; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D017678:Sex Distribution; D013624:Taiwan / Q000453:epidemiology
chemical_list: D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)