Homocysteine and methylenetetrahydrofolate reductase genotype: association with risk of coronary heart disease and relation to inflammatory, hemostatic, and lipid parameters.
OBJECTIVE
It has been suggested that homocysteine (tHcy) levels and methylenetetrahydrofolate reductase (MTHFR) genotype are primary risk factors for coronary heart disease (CHD). We performed a case-control study to investigate whether tHcy levels and MTHFR genotype (677 C-->T mutation and 1298 A-->C mutation) are associated with CHD under special consideration of the possibility for confounding.


METHODS
German speaking patients aged 40-68 years who underwent coronary angiography at the University of Ulm between April 1996 and November 1997 and who had at least one coronary stenosis greater than 50% were included in the study. Controls were sampled from voluntary blood donors and were matched for sex and age. tHcy levels were measured by high performance liquid chromatography and MTHFR genotype by means of polymerase chain reaction. In addition, C-reactive protein, fibrinogen, plasma viscosity, leukocytes, HDL-cholesterol and Lp(a) were determined.


RESULTS
Overall, 312 patients and 479 controls were enrolled in the study (response in patients 78%, in controls 84%). Mean tHcy value was 9.43 micromol/l in CHD patients and 8.91 micromol/l in controls (P=0.145). Prevalence of 677TT-polymorphism was 9.9% in patients and 10.4% in controls (P=0.295). Prevalence of 1298CC-polymorphism was 9.7% in patients and 13.8% in controls (P=0.346). There was a clear association of tHcy-values, but not of 677TT- or 1298CC-genotype with conventional CHD risk factors. After adjustment for these risk factors no increased risk for CHD could be associated with increased tHcy-values, with 677TT or 1298CC-genotype, or with their combination. Also no statistically significant relationships of these parameters to inflammatory, rheologic or hemostatic parameters or lipids were detectable.


CONCLUSIONS
These results do not confirm an independent relationship of tHcy values and MTHFR genotype with risk of CHD in the population studied.
Rothenbacher
D
D
Department of Epidemiology, The German Centre for Research on Ageing, Heidelberg, Germany.
Fischer
H G
HG
Hoffmeister
A
A
Hoffmann
M M
MM
März
W
W
Bode
G
G
Rosenthal
J
J
Koenig
W
W
Brenner
H
H
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D017023:Coronary Angiography; D003327:Coronary Disease / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006487:Hemostasis; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000097:blood* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D015995:Prevalence; D012307:Risk Factors
D005819:Genetic Markers; D008055:Lipids; D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)