Q192R polymorphism of the paraoxanase 1 gene and its association with serum lipoprotein variables and carotid artery intima-media thickness in young adults from a biracial community. The Bogalusa Heart Study.
Paraoxanase (PON 1), a high-density lipoprotein-associated enzyme, exerts an antiatherogenic effect by protecting low-density lipoproteins (LDL) against oxidation. A common polymorphism at codon 192(Q/R) of the PON 1 gene has been shown to be associated with an adverse lipoprotein profile and increased coronary artery disease (CAD) risk. However, these observations are based mostly on case-control studies involving relatively older adults. This study examined the frequency and phenotypic (lipoprotein variables) effect of the Q192R variant in a community-based sample of 1786 black and white young adults (mean age: 32.5 years; 69% white, 44% males). In addition, the genotypic effect of this polymorphism on ultrasonographically measured carotid artery intima-media thickness (IMT), a surrogate measure of CAD risk, was examined in a subsample of 436 young adults (mean age: 32.6 years; 70% white, 42% male). The frequency of the variant allele (R192) was higher in blacks than in whites (0.668 versus 0.297, P <0.001). After adjusting for age, sex, body mass index, and smoking status, the R versus Q allele was associated with increased HDL cholesterol in whites (P=0.041), whereas the opposite was true in blacks (P=0.008). Neither the Q nor the R allele was associated with LDL cholesterol and triglycerides in both races. The genotypic effect on the carotid IMT adjusted for the covariates including lipoprotein variables was not apparent in whites or blacks. However, among whites, the carotid IMT was lower in carriers (QR + R) versus non-carriers (QQ) of the variant allele among females (P=0.008) and non-smokers (P=0.026). In addition, the variant allele negated the adverse positive relationship between the carotid IMT and triglycerides among whites (P=0.212 for carriers versus P <0.001 for non-carriers). These results indicate a differential effect of the Q192R variant on HDL cholesterol in whites versus blacks and a beneficial interaction effect of the variant allele with individual's sex, smoking status or triglyceride levels on the carotid IMT among whites.
Tulane Center for Cardiovascular Health and Department of Epidemiology, Tulane School of Public Health and Tropical Medicine, 1440 Canal Street, 18th floor (SL-12), New Orleans, LA 70112, USA.
Sathanur R
SR
Srinivasan
Shengxu
S
Li
Wei
W
Chen
Rong
R
Tang
M Gene
MG
Bond
Eric
E
Boerwinkle
Gerald S
GS
Berenson
D000293:Adolescent; D000328:Adult; D043303:Aryldialkylphosphatase / Q000235:genetics*; D044383:Black People; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics; D002339:Carotid Arteries / Q000473:pathology*; D002784:Cholesterol / Q000097:blood*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014280:Triglycerides / Q000097:blood*; D017539:Tunica Intima / Q000473:pathology*; D017540:Tunica Media / Q000473:pathology*; D044465:White People
D014280:Triglycerides; D002784:Cholesterol; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human