Gln-Arg192 polymorphism of paraoxonase and coronary heart disease in type 2 diabetes.
Paraoxonase is a high-density-lipoprotein-associated enzyme capable of hydrolysing lipid peroxides. Thus it might protect lipoproteins from oxidation. It has two isoforms, which arise from a glutamine (A isoform) to arginine (B isoform) interchange at position 192. The relevance of this polymorphism to coronary heart disease (CHD) in non-insulin-dependent diabetic patients was investigated in case-control study. Of the 434 patients, 171 had confirmed coronary artery disease; the other 263 had no history of such disease. The B allele and AB+BB genotypes were associated with an increased risk of coronary heart disease. Compared with subjects homozygous for the A allele (AA genotype), the odds ratio of CHD for subjects homozygous for the B allele was 2.5 (95% CI 1.2-5.3) and that for those heterozygous for the B allele was 1.6 (95% CI 1.1-2.4), suggesting a codominant effect on cardiovascular risk. When subjected to multivariate analysis, the B allele remained significantly associated with CHD (odds ratio 1.94, p = 0.03). The paraoxonase gene polymorphism is thus an independent cardiovascular risk factor in non-insulin-dependent diabetic patients. A possible explanation for this finding is that activity of the paraoxonase B isotype does not protect well against lipid oxidation, a major atherogenic pathway.
Ruiz
J
J
Division d'Epidémiologie Clinique, Geneva University Hospital, Switzerland.
Blanché
H
H
James
R W
RW
Garin
M C
MC
Vaisse
C
C
Charpentier
G
G
Cohen
N
N
Morabia
A
A
Passa
P
P
Froguel
P
P
D001120:Arginine; D043303:Aryldialkylphosphatase; D016022:Case-Control Studies; D003327:Coronary Disease / Q000150:complications / Q000201:enzymology* / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000201:enzymology*; D004950:Esterases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D005973:Glutamine; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012307:Risk Factors
D005973:Glutamine; D001120:Arginine; D004950:Esterases; D043303:Aryldialkylphosphatase