Skip to main content
Erschienen in: Herz 7/2018

23.08.2017 | Original articles

PON1 L55M and Q192R gene polymorphisms and CAD risks in patients with hyperlipidemia

Clinical study of possible associations

verfasst von: H. Chen, M.M, S. Ding, M.M, M. Zhou, M.B, X. Wu, M.B, X. Liu, M.D, J. Liu, M.M, Y. Wu, M.M, D. Liu, M.B

Erschienen in: Herz | Ausgabe 7/2018

Einloggen, um Zugang zu erhalten

Abstract

Objective

A decreased plasma high density lipoprotein (HDL) cholesterol level is a strong risk factor for coronary artery disease (CAD). Antioxidant activity of HDL mainly lies in the activity of paraoxonase (PON). This study aimed to investigate the relationships between PON1 L55M and Q192R polymorphisms, and the risks of CAD in patients with hyperlipidemia.

Methods

From January 2014 to January 2016, 244 patients were divided into hyperlipidemia, hyperlipidemia + CAD, and control groups. The hyperlipidemia and hyperlipidemia + CAD groups were designated as the case group. Serum PON1 concentrations were measured using the enzyme-linked immunosorbent assay. After isolating genomic DNA, the PON1 L55M and Q192R genes were amplified by polymerase chain reaction and sequenced.

Results

In the case group, the genotypes LM and LL were detected significantly more often than in the control group, as were the alleles R (33.33%, 42.12%) and L (22.78%, 29.11%). The frequency of QR and RR genotypes was significantly higher in the hyperlipidemia + CAD group than in the hyperlipidemia group; the allele R in the hyperlipidemia + CAD group (42.77%) was more frequent than in the hyperlipidemia group (23.78%). The Q192R polymorphism was associated with low serum PON1 concentrations, and the lowest concentration was observed in the 192QR + 192RR genotype (P = 0.03). Logistic regression analysis showed a significant correlation between the 192R allele and smoking (P = 0.03), body mass index (P = 0.02), systolic blood pressure (P = 0.004), total cholesterol (P = 0.03), triglycerides (P = 0.01), HDL (P = 0.004), and low density lipoprotein (P = 0.02).

Conclusion

The PON1 alleles 192R and 55L are associated with CAD, and the Q192R polymorphism may be a risk factor for CAD.
Literatur
1.
Zurück zum Zitat Agrawal S, Tripathi G, Prajnya R et al (2009) Paraoxonase 1 gene polymorphisms contribute to coronary artery disease risk among north Indians. Indian J Med Sci 63:335–344CrossRef Agrawal S, Tripathi G, Prajnya R et al (2009) Paraoxonase 1 gene polymorphisms contribute to coronary artery disease risk among north Indians. Indian J Med Sci 63:335–344CrossRef
2.
Zurück zum Zitat Altuner D, Ates I, Suzen SH et al (2011) The relationship of PON1 QR 192 and LM 55 polymorphisms with serum paraoxonase activities of Turkish diabetic patients. Toxicol Ind Health 27:873–878CrossRef Altuner D, Ates I, Suzen SH et al (2011) The relationship of PON1 QR 192 and LM 55 polymorphisms with serum paraoxonase activities of Turkish diabetic patients. Toxicol Ind Health 27:873–878CrossRef
3.
Zurück zum Zitat Androutsopoulos VP, Kanavouras K, Tsatsakis AM (2011) Role of paraoxonase 1 (PON1) in organophosphate metabolism: implications in neurodegenerative diseases. Toxicol Appl Pharmacol 256:418–424CrossRef Androutsopoulos VP, Kanavouras K, Tsatsakis AM (2011) Role of paraoxonase 1 (PON1) in organophosphate metabolism: implications in neurodegenerative diseases. Toxicol Appl Pharmacol 256:418–424CrossRef
4.
Zurück zum Zitat Arca M, Ombres D, Montali A et al (2002) PON1 L55M polymorphism is not a predictor of coronary atherosclerosis either alone or in combination with Q192R polymorphism in an Italian population. Eur J Clin Invest 32:9–15CrossRef Arca M, Ombres D, Montali A et al (2002) PON1 L55M polymorphism is not a predictor of coronary atherosclerosis either alone or in combination with Q192R polymorphism in an Italian population. Eur J Clin Invest 32:9–15CrossRef
5.
Zurück zum Zitat Blatter Garin MC, Moren X, James RW (2006) Paraoxonase-1 and serum concentrations of HDL-cholesterol and apoA-I. J Lipid Res 47:515–520CrossRef Blatter Garin MC, Moren X, James RW (2006) Paraoxonase-1 and serum concentrations of HDL-cholesterol and apoA-I. J Lipid Res 47:515–520CrossRef
6.
Zurück zum Zitat Chang TI, Streja E, Moradi H (2017) Could high-density lipoprotein cholesterol predict increased cardiovascular risk? Curr Opin Endocrinol Diabetes Obes 24:140–147CrossRef Chang TI, Streja E, Moradi H (2017) Could high-density lipoprotein cholesterol predict increased cardiovascular risk? Curr Opin Endocrinol Diabetes Obes 24:140–147CrossRef
7.
Zurück zum Zitat Dasgupta S, Demirci FY, Dressen AS et al (2011) Association analysis of PON2 genetic variants with serum paraoxonase activity and systemic lupus erythematosus. BMC Med Genet 12:7CrossRef Dasgupta S, Demirci FY, Dressen AS et al (2011) Association analysis of PON2 genetic variants with serum paraoxonase activity and systemic lupus erythematosus. BMC Med Genet 12:7CrossRef
8.
Zurück zum Zitat Fedele F, Mancone M, Chilian WM et al (2013) Role of genetic polymorphisms of ion channels in the pathophysiology of coronary microvascular dysfunction and ischemic heart disease. Basic Res Cardiol 108:387CrossRef Fedele F, Mancone M, Chilian WM et al (2013) Role of genetic polymorphisms of ion channels in the pathophysiology of coronary microvascular dysfunction and ischemic heart disease. Basic Res Cardiol 108:387CrossRef
9.
Zurück zum Zitat Ferrari R, Fox K (2016) Heart rate reduction in coronary artery disease and heart failure. Nat Rev Cardiol 13:493–501CrossRef Ferrari R, Fox K (2016) Heart rate reduction in coronary artery disease and heart failure. Nat Rev Cardiol 13:493–501CrossRef
10.
Zurück zum Zitat Ferre N, Tous M, Paul A et al (2002) Paraoxonase Gln-Arg(192) and Leu-Met(55) gene polymorphisms and enzyme activity in a population with a low rate of coronary heart disease. Clin Biochem 35:197–203CrossRef Ferre N, Tous M, Paul A et al (2002) Paraoxonase Gln-Arg(192) and Leu-Met(55) gene polymorphisms and enzyme activity in a population with a low rate of coronary heart disease. Clin Biochem 35:197–203CrossRef
11.
Zurück zum Zitat Gupta N, Binu KB, Singh S et al (2012) Low serum PON1 activity: an independent risk factor for coronary artery disease in North-West Indian type 2 diabetics. Gene 498:13–19CrossRef Gupta N, Binu KB, Singh S et al (2012) Low serum PON1 activity: an independent risk factor for coronary artery disease in North-West Indian type 2 diabetics. Gene 498:13–19CrossRef
12.
Zurück zum Zitat Ikram MK, Sim X, Jensen RA et al (2010) Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo. Plos Genet 6:e1001184CrossRef Ikram MK, Sim X, Jensen RA et al (2010) Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo. Plos Genet 6:e1001184CrossRef
13.
Zurück zum Zitat Imai Y, Morita H, Kurihara H et al (2000) Evidence for association between paraoxonase gene polymorphisms and atherosclerotic diseases. Atherosclerosis 149:435–442CrossRef Imai Y, Morita H, Kurihara H et al (2000) Evidence for association between paraoxonase gene polymorphisms and atherosclerotic diseases. Atherosclerosis 149:435–442CrossRef
14.
Zurück zum Zitat Ito T, Yasue H, Yoshimura M et al (2002) Paraoxonase gene Gln192Arg (Q192R) polymorphism is associated with coronary artery spasm. Hum Genet 110:89–94CrossRef Ito T, Yasue H, Yoshimura M et al (2002) Paraoxonase gene Gln192Arg (Q192R) polymorphism is associated with coronary artery spasm. Hum Genet 110:89–94CrossRef
15.
Zurück zum Zitat Ko YL, Ko YS, Wang SM et al (1998) The Gln-Arg 191 polymorphism of the human paraoxonase gene is not associated with the risk of coronary artery disease among Chinese in Taiwan. Atherosclerosis 141:259–264CrossRef Ko YL, Ko YS, Wang SM et al (1998) The Gln-Arg 191 polymorphism of the human paraoxonase gene is not associated with the risk of coronary artery disease among Chinese in Taiwan. Atherosclerosis 141:259–264CrossRef
16.
Zurück zum Zitat Kuremoto K, Watanabe Y, Ohmura H et al (2003) R/R genotype of human paraoxonase (PON1) is more protective against lipoprotein oxidation and coronary artery disease in Japanese subjects. J Atheroscler Thromb 10:85–92CrossRef Kuremoto K, Watanabe Y, Ohmura H et al (2003) R/R genotype of human paraoxonase (PON1) is more protective against lipoprotein oxidation and coronary artery disease in Japanese subjects. J Atheroscler Thromb 10:85–92CrossRef
17.
Zurück zum Zitat Lawlor DA, Day IN, Gaunt TR et al (2004) The association of the PON1 Q192R polymorphism with coronary heart disease: findings from the British Women’s Heart and Health cohort study and a meta-analysis. Bmc Genet 5:17CrossRef Lawlor DA, Day IN, Gaunt TR et al (2004) The association of the PON1 Q192R polymorphism with coronary heart disease: findings from the British Women’s Heart and Health cohort study and a meta-analysis. Bmc Genet 5:17CrossRef
18.
Zurück zum Zitat Likidlilid A, Akrawinthawong K, Poldee S et al (2010) Paraoxonase 1 polymorphisms as the risk factor of coronary heart disease in a Thai population. Acta Cardiol 65:681–691CrossRef Likidlilid A, Akrawinthawong K, Poldee S et al (2010) Paraoxonase 1 polymorphisms as the risk factor of coronary heart disease in a Thai population. Acta Cardiol 65:681–691CrossRef
19.
Zurück zum Zitat Luu HN, Kingah PL, North K et al (2011) Interaction of folate intake and the paraoxonase Q192R polymorphism with risk of incident coronary heart disease and ischemic stroke: the atherosclerosis risk in communities study. Ann Epidemiol 21:815–823CrossRef Luu HN, Kingah PL, North K et al (2011) Interaction of folate intake and the paraoxonase Q192R polymorphism with risk of incident coronary heart disease and ischemic stroke: the atherosclerosis risk in communities study. Ann Epidemiol 21:815–823CrossRef
20.
Zurück zum Zitat Mackness B, Mackness MI, Arrol S et al (1998) Effect of the human serum paraoxonase 55 and 192 genetic polymorphisms on the protection by high density lipoprotein against low density lipoprotein oxidative modification. FEBS Lett 423:57–60CrossRef Mackness B, Mackness MI, Arrol S et al (1998) Effect of the human serum paraoxonase 55 and 192 genetic polymorphisms on the protection by high density lipoprotein against low density lipoprotein oxidative modification. FEBS Lett 423:57–60CrossRef
21.
Zurück zum Zitat Mackness B, Marsillach J, Elkeles RS et al (2012) Paraoxonase-1 is not associated with coronary artery calcification in type 2 diabetes: results from the PREDICT study. Dis Markers 33:101–112CrossRef Mackness B, Marsillach J, Elkeles RS et al (2012) Paraoxonase-1 is not associated with coronary artery calcification in type 2 diabetes: results from the PREDICT study. Dis Markers 33:101–112CrossRef
22.
Zurück zum Zitat Mcpherson R (2010) Chromosome 9p21 and coronary artery disease. N Engl J Med 362:1736–1737CrossRef Mcpherson R (2010) Chromosome 9p21 and coronary artery disease. N Engl J Med 362:1736–1737CrossRef
23.
Zurück zum Zitat Mohamed RH, Karam RA, Abd El-Aziz TA (2010) The relationship between paraoxonase1-192 polymorphism and activity with coronary artery disease. Clin Biochem 43:553–558CrossRef Mohamed RH, Karam RA, Abd El-Aziz TA (2010) The relationship between paraoxonase1-192 polymorphism and activity with coronary artery disease. Clin Biochem 43:553–558CrossRef
24.
Zurück zum Zitat Otani H (2011) Oxidative stress as pathogenesis of cardiovascular risk associated with metabolic syndrome. Antioxid Redox Signal 15:1911–1926CrossRef Otani H (2011) Oxidative stress as pathogenesis of cardiovascular risk associated with metabolic syndrome. Antioxid Redox Signal 15:1911–1926CrossRef
25.
Zurück zum Zitat Precourt LP, Amre D, Denis MC et al (2011) The three-gene paraoxonase family: physiologic roles, actions and regulation. Atherosclerosis 214:20–36CrossRef Precourt LP, Amre D, Denis MC et al (2011) The three-gene paraoxonase family: physiologic roles, actions and regulation. Atherosclerosis 214:20–36CrossRef
26.
Zurück zum Zitat Ravera A, Carubelli V, Sciatti E et al (2016) Nutrition and cardiovascular disease: finding the perfect recipe for cardiovascular health. Nutrients 8(6):363CrossRef Ravera A, Carubelli V, Sciatti E et al (2016) Nutrition and cardiovascular disease: finding the perfect recipe for cardiovascular health. Nutrients 8(6):363CrossRef
27.
Zurück zum Zitat Regieli JJ, Jukema JW, Doevendans PA et al (2009) Paraoxonase variants relate to 10-year risk in coronary artery disease: impact of a high-density lipoprotein-bound antioxidant in secondary prevention. J Am Coll Cardiol 54:1238–1245CrossRef Regieli JJ, Jukema JW, Doevendans PA et al (2009) Paraoxonase variants relate to 10-year risk in coronary artery disease: impact of a high-density lipoprotein-bound antioxidant in secondary prevention. J Am Coll Cardiol 54:1238–1245CrossRef
28.
Zurück zum Zitat Rejeb J, Omezzine A, Rebhi L et al (2013) Association of PON1 and PON2 polymorphisms with PON1 activity and significant coronary stenosis in a Tunisian population. Biochem Genet 51:76–91CrossRef Rejeb J, Omezzine A, Rebhi L et al (2013) Association of PON1 and PON2 polymorphisms with PON1 activity and significant coronary stenosis in a Tunisian population. Biochem Genet 51:76–91CrossRef
29.
Zurück zum Zitat Rios DL, D’onofrio LO, Cerqueira CC et al (2007) Paraoxonase 1 gene polymorphisms in angiographically assessed coronary artery disease: evidence for gender interaction among Brazilians. Clin Chem Lab Med 45:874–878CrossRef Rios DL, D’onofrio LO, Cerqueira CC et al (2007) Paraoxonase 1 gene polymorphisms in angiographically assessed coronary artery disease: evidence for gender interaction among Brazilians. Clin Chem Lab Med 45:874–878CrossRef
30.
Zurück zum Zitat Shenhar-Tsarfaty S, Waiskopf N, Ofek K et al (2013) Atherosclerosis and arteriosclerosis parameters in stroke patients associate with paraoxonase polymorphism and esterase activities. Eur J Neurol 20:891–898CrossRef Shenhar-Tsarfaty S, Waiskopf N, Ofek K et al (2013) Atherosclerosis and arteriosclerosis parameters in stroke patients associate with paraoxonase polymorphism and esterase activities. Eur J Neurol 20:891–898CrossRef
31.
Zurück zum Zitat Tune JD, Goodwill AG, Sassoon DJ et al (2017) Cardiovascular consequences of metabolic syndrome. Transl Res 183:57–70CrossRef Tune JD, Goodwill AG, Sassoon DJ et al (2017) Cardiovascular consequences of metabolic syndrome. Transl Res 183:57–70CrossRef
32.
Zurück zum Zitat Wang M, Lang X, Zou L et al (2011) Four genetic polymorphisms of paraoxonase gene and risk of coronary heart disease: a meta-analysis based on 88 case-control studies. Atherosclerosis 214:377–385CrossRef Wang M, Lang X, Zou L et al (2011) Four genetic polymorphisms of paraoxonase gene and risk of coronary heart disease: a meta-analysis based on 88 case-control studies. Atherosclerosis 214:377–385CrossRef
33.
Zurück zum Zitat Yoshino S, Cilluffo R, Best PJ et al (2014) Single nucleotide polymorphisms associated with abnormal coronary microvascular function. Coron Artery Dis 25:281–289CrossRef Yoshino S, Cilluffo R, Best PJ et al (2014) Single nucleotide polymorphisms associated with abnormal coronary microvascular function. Coron Artery Dis 25:281–289CrossRef
34.
Zurück zum Zitat Zama T, Murata M, Matsubara Y et al (1997) A 192Arg variant of the human paraoxonase (HUMPONA) gene polymorphism is associated with an increased risk for coronary artery disease in the Japanese. Arterioscler Thromb Vasc Biol 17:3565–3569CrossRef Zama T, Murata M, Matsubara Y et al (1997) A 192Arg variant of the human paraoxonase (HUMPONA) gene polymorphism is associated with an increased risk for coronary artery disease in the Japanese. Arterioscler Thromb Vasc Biol 17:3565–3569CrossRef
35.
Zurück zum Zitat Zhao Y, Ma Y, Fang Y et al (2012) Association between PON1 activity and coronary heart disease risk: a meta-analysis based on 43 studies. Mol Genet Metab 105:141–148CrossRef Zhao Y, Ma Y, Fang Y et al (2012) Association between PON1 activity and coronary heart disease risk: a meta-analysis based on 43 studies. Mol Genet Metab 105:141–148CrossRef
Metadaten
Titel
PON1 L55M and Q192R gene polymorphisms and CAD risks in patients with hyperlipidemia
Clinical study of possible associations
verfasst von
H. Chen, M.M
S. Ding, M.M
M. Zhou, M.B
X. Wu, M.B
X. Liu, M.D
J. Liu, M.M
Y. Wu, M.M
D. Liu, M.B
Publikationsdatum
23.08.2017
Verlag
Springer Medizin
Erschienen in
Herz / Ausgabe 7/2018
Print ISSN: 0340-9937
Elektronische ISSN: 1615-6692
DOI
https://doi.org/10.1007/s00059-017-4611-0

Weitere Artikel der Ausgabe 7/2018

Herz 7/2018 Zur Ausgabe

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.