Interaction of CA repeat polymorphism of the endothelial nitric oxide synthase and hyperhomocysteinemia in acute coronary syndromes: evidence of gender-specific differences.
We have recently shown that high CA repeat copy numbers (> or = 34 repeats) in intron 13 of the endothelial nitric oxide (eNOS) gene are associated with excess risk of coronary artery disease. Hyperhomocysteinemia interacts by several mechanisms with the NO system, thereby favoring endothelial dysfunction. Since hyperhomocysteinemia evidently promotes prothrombotic activation, we investigated a possible interaction among hyperhomocysteinemia, the eNOS CA repeat polymorphism, and acute coronary syndromes. The median value of homocysteine in our study population was 9.4 micromol/l. We accordingly determined the relative risk of acute coronary syndromes for homocysteine values higher than 9.4 micromol/l and 9.4 micromol/l or lower in the entire coronary artery disease group, and at different CA repeat cutoff values (34, 35, 36, 37, 38 CA repeats). For the entire coronary artery disease group ( n=1000), homocysteine levels higher than 9.4 micromol/l were not significantly associated with acute coronary syndromes. Although the CA repeat copy numbers were not associated with acute coronary syndromes in the overall group, the relative risk among women with homocysteine higher than 9.4 micromol/l for developing acute coronary syndromes increased nonsignificantly from 0.98 at cutoff 34 CA repeats to 1.68 at 35 CA repeats and significantly to 4.89 at 36 CA repeats, 11.20 at 37 CA repeats, and 18.32 at 38 CA repeats. This effect modification was not observed in men. These data suggest gender-specific gene-environment interaction between the CA repeat eNOS polymorphism and homocysteine in acute coronary syndromes.
Laule
Michael
M
Medizinische Klinik mit Schwerpunkt Kardiologie, Angiologie, Pneumologie, Charité, Campus Mitte, Humboldt-Universität, Schumannstrasse 21/21, 10117 Berlin, Germany.
Meisel
Christian
C
Prauka
Ines
I
Cascorbi
Ingolf
I
Malzahn
Uwe
U
Felix
Stephan B
SB
Baumann
Gert
G
Roots
Ivar
I
Stangl
Karl
K
Stangl
Verena
V
D000208:Acute Disease; D016022:Case-Control Studies; D018900:Dinucleotide Repeats; D005260:Female; D006331:Heart Diseases / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications* / Q000453:epidemiology; D008297:Male; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D011110:Polymorphism, Genetic; D012737:Sex Factors; D013577:Syndrome
C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III