The signal sequence polymorphism of the MnSOD gene is associated with the degree of carotid atherosclerosis.
Redox-state of the cells of vascular walls is an important determinant of atherosclerosis. Manganese superoxide dismutase (MnSOD) is an essential anti-oxidant enzyme working in mitochondria of mammalian cells. A potentially functional amino acid polymorphism (Ala16Val) has been described in the signal sequence of the enzyme. The aim of the current study was to test whether the signal sequence polymorphism of the MnSOD would be associated with the degree of carotid atherosclerosis. The polymorphism was genotyped in a sample of 989 middle-aged hypertensive and control subjects. Carotid atherosclerosis was quantified as intima-media thickness (IMT) by ultrasound. The signal sequence polymorphism was found to be a minor determinant of carotid IMT explaining 1.3% of the overall variation, the Val allele associated with the higher IMT. In women, a significant interaction with plasma levels of low-density lipoprotein (LDL) cholesterol was detected, since LDL cholesterol levels were positively correlated with carotid IMT only in the carriers of the Val allele and the Val allele was associated with higher IMT only in the subjects with highest plasma levels of LDL cholesterol. In conclusion, the signal sequence polymorphism of the MnSOD gene is a minor determinant of carotid IMT pointing out the importance of redox-balance in the atherogenesis.
Department of Internal Medicine and Biocenter Oulu, University of Oulu, P.O. 5000, Finland. sakari.kakko@oulu.fi
Sakari
S
Kakko
Markku
M
Päivänsalo
Pirjo
P
Koistinen
Y Antero
YA
Kesäniemi
Vuokko L
VL
Kinnula
Markku J
MJ
Savolainen
D000328:Adult; D000483:Alleles; D015992:Body Mass Index; D002340:Carotid Artery Diseases / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D017536:Carotid Artery, Common / Q000201:enzymology* / Q000473:pathology*; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005387:Finland; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D021382:Protein Sorting Signals / Q000235:genetics*; D012307:Risk Factors; D012720:Severity of Illness Index; D013223:Statistics as Topic; D013482:Superoxide Dismutase / Q000235:genetics*; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology
D008078:Cholesterol, LDL; D021382:Protein Sorting Signals; D013482:Superoxide Dismutase