Association of the manganese superoxide dismutase polymorphism with vasospastic angina pectoris.
BACKGROUND
Vasospastic angina (VSA) is closely related to endothelial dysfunction caused by oxidative damage. Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme that functions in mitochondria. There are two genetic variants of MnSOD arising from a substitution of an alanine for a valine in the signal peptide. We previously reported that the valine allele of MnSOD decreases the mitochondrial MnSOD (mtMnSOD) activity. Here, we investigated the association of the MnSOD polymorphism (Ala16Val) with VSA.


RESULTS
Blood samples were collected from 618 healthy subjects who did not have any symptoms or other evidence suggesting angina pectoris, and 228 patients who underwent coronary angiography on suspicion of angina, and were diagnosed to have VSA by acetylcholine test. MnSOD genotype of each subject was determined by real-time polymerase chain reaction. The valine allele frequency was higher in the VSA patients (0.890) than in the healthy subjects (0.839) [odds ratio (OR)=1.55, p=0.0085]. In healthy subjects the MnSOD genotype distribution was as follows: alanine/alanine 1.9%, alanine/valine 28.3%, and valine/valine 69.8%, and in VSA patients the prevalence was: alanine/alanine 1.3%, alanine/valine 19.3%, and valine/valine 79.4%. Thus, the valine allele was closely associated with VSA (p=0.019). Multivariate logistic regression analysis showed valine/valine homozygosity to be an independent risk factor for VSA (OR=2.02, 95% CI 1.43, 2.85; p=0.0012).


CONCLUSIONS
The valine variant of MnSOD signal peptide increases the risk of VSA.
Fujimoto
Hajime
H
Department of Cardiovascular Medicine, Toranomon Hospital, 2-2-2, Toranomon, Minato-ku, Tokyo, Japan. hafujimoto-circ@umin.ac.jp
Kobayashi
Hisae
H
Ogasawara
Ken
K
Yamakado
Minoru
M
Ohno
Minoru
M
D000788:Angina Pectoris, Variant / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics*
D013482:Superoxide Dismutase