Sara Saffar Soflaei1, Mojtaba Baktashian1, Kiana Hosseinpour Moghaddam2, Maryam Saberi-Karimian3, Negin Kosari1, Seyed Mohammad Hashemi4, Mohsen Mouhebati5, Mahsa Amini1, Mashallah Dehghani5, Habibollah Esmaily6, Mahmoud Ebrahimi5, Homa Falsoleiman5, Abolfazl Nosrati-Tirkani7, Fatemeh Sadabadi1, Gordon A Ferns8, Mansoor Salehi9, Alireza Pasdar1,10, Majid Ghayour-Mobarhan3,5. 1. International UNESCO Center for Health-Related Basic Sciences and Human Nutrition , Mashhad University of Medical Sciences , Mashhad - Irã. 2. Department of Biology , Faculty of Sciences , Ferdowsi University of Mashhad , Mashhad - Irã. 3. Metabolic Syndrome Research Center , Faculty of Medicine , Mashhad University of Medical Sciences , Mashhad - Irã. 4. Department of Cardiology , Chamran Hospital, School of Medicine , Isfahan University of Medical Sciences , Isfahan - Irã. 5. Cardiovascular Research Center , School of Medicine , Mashhad University of Medical Sciences , Mashhad - Irã. 6. Department of Biostatistics and Epidemiology , School of Health , Mashhad University of Medical Sciences , Mashhad - Irã. 7. Biochemistry of Nutrition Research Center , Faculty of Medicine , Mashhad University of Medical Sciences , Mashhad - Irã. 8. Brighton & Sussex Medical School , Division of Medical Education , Falmer, Brighton - Reino Unido. 9. Department of genetics , Faculty of medicine and genetics laboratory AL Zahra hospital , Isfahan University of Medicine , Isfahan - Irã. 10. Division of Applied Medicine , Medical School , University of Aberdeen , Foresterhill, Aberdeen - Reino Unido.
Abstract
BACKGROUND: It has been shown that increased serum PON1 levels are protective against several disorders. Several single nucleotide polymorphisms (SNPs) of the PON1 gene have been reported to be associated with serum enzyme protein levels and activity. OBJECTIVE: To investigate the association of SNPs of PON1 and serum paraoxonase activity with coronary artery disease (CAD). METHODS: A total of 601 unrelated patients who underwent coronary angiography including those who had >50% stenosis (N=266) and those with <30% stenosis (N=335) were studied. The Paraoxonase gene rs662 and rs840560 SNPs were determined using the ARMS-PCR method and the rs705379 SNP was genotyped using PCR-RFLP analysis. Serum paraoxonase activity was measured using paraoxon as a substrate. A p value of p<0.05 was considered as significant. RESULTS: Serum paraoxonase activity was not significantly different between the study groups. After adjustment for age, sex, hypertension, diabetes mellitus and dyslipidemia, the GG genotype and co-dominant model of rs662 was positively associated with a positive angiogram (respectively, OR=2.424, 95%CI [1.123-5.233], p<0.05, OR=1.663, 95%CI [1.086-2.547]). Serum paraoxonase activity was significantly higher in the G allele and GG variant of rs662, A allele and AA variant of rs854560 and C allele and CC variant of rs705379. The haplotype analysis has shown that the ATC haplotype was significantly more prevalent among the angiogram negative group. The analysis between groups indicated that the A allele of rs662 was significantly associated with lower paraoxonase activity in the positive angiogram group (p=0.019). CONCLUSIONS: The presence of the G allele of the rs662 single nucleotide polymorphism is independently associated to increased risk of CAD.
BACKGROUND: It has been shown that increased serum PON1 levels are protective against several disorders. Several single nucleotide polymorphisms (SNPs) of the PON1 gene have been reported to be associated with serum enzyme protein levels and activity. OBJECTIVE: To investigate the association of SNPs of PON1 and serum paraoxonase activity with coronary artery disease (CAD). METHODS: A total of 601 unrelated patients who underwent coronary angiography including those who had >50% stenosis (N=266) and those with <30% stenosis (N=335) were studied. The Paraoxonase gene rs662 and rs840560 SNPs were determined using the ARMS-PCR method and the rs705379 SNP was genotyped using PCR-RFLP analysis. Serum paraoxonase activity was measured using paraoxon as a substrate. A p value of p<0.05 was considered as significant. RESULTS: Serum paraoxonase activity was not significantly different between the study groups. After adjustment for age, sex, hypertension, diabetes mellitus and dyslipidemia, the GG genotype and co-dominant model of rs662 was positively associated with a positive angiogram (respectively, OR=2.424, 95%CI [1.123-5.233], p<0.05, OR=1.663, 95%CI [1.086-2.547]). Serum paraoxonase activity was significantly higher in the G allele and GG variant of rs662, A allele and AA variant of rs854560 and C allele and CC variant of rs705379. The haplotype analysis has shown that the ATC haplotype was significantly more prevalent among the angiogram negative group. The analysis between groups indicated that the A allele of rs662 was significantly associated with lower paraoxonase activity in the positive angiogram group (p=0.019). CONCLUSIONS: The presence of the G allele of the rs662 single nucleotide polymorphism is independently associated to increased risk of CAD.
Authors: Daniel S Kim; Amber A Burt; Jane E Ranchalis; Rebecca J Richter; Julieann K Marshall; Karen S Nakayama; Ella R Jarvik; Jason F Eintracht; Elisabeth A Rosenthal; Clement E Furlong; Gail P Jarvik Journal: J Lipid Res Date: 2012-08-15 Impact factor: 5.922
Authors: Alexandros Zafiropoulos; Manolis Linardakis; Eugene H J M Jansen; Aristidis M Tsatsakis; Antonis Kafatos; George N Tzanakakis Journal: J Lipid Res Date: 2010-02-03 Impact factor: 5.922