Paraoxonase 1 Gene L55M Polymorphism and Paraoxonase 1 Activity in Obstructive Sleep Apnea Patients
The antioxidant enzyme paraoxonase-1 (PON1) may limit oxidative stress in the development of cardiovascular diseases (CVD) and obstructive sleep apnea (OSA). The aim of the study was to determine PON1 gene L55M polymorphism in OSA-positive and OSA-negative subjects, along with paraoxonase activity of the enzyme (PON1-act). Caucasians aged 25–75, with BMI 19.0–53.0 kg/m2 and no acute or severe chronic disorder underwent polysomnography, and OSA-negative (n = 44) and OSA-positive (n = 57) groups were established. The following parameters were assessed: arterial blood pressure and serum glucose, lipids, C–reactive protein, and homocysteine. Genomic DNA was extracted and amplified, and automatic sequencing was used to confirm the LL, LM, MM genotypes. PON1–act was measured spectrophotometrically using paraoxon as a substrate. We found that frequency of polymorphisms differed significantly between the OSA–negative and OSA–positive patients (p < 0.05). Increased PON1–act was observed in the LL–genotype versus the LM + MM–genotype in the study population (p < 0.05). PON1–act was higher in the OSA–negative compared with OSA–positive patients (p < 0.001); in general and in the subgroups presenting the LL or LM genotype. In addition, there was an inverse relationship between PON1–act and LDL–cholesterol in the entire study population. The OSA–positive group presented an inverse relationship between PON1–act and fasting glucose. We conclude that patients could benefit from the LL genotype related with higher activity of PON1. OSA pathology might decrease the enzyme activity, despite the presence of L allele.
KeywordsAntioxidant activity Atherosclerosis Gene polymorphism Oxidative stress Paraoxonase enzyme Obstructive sleep apnea
Conflicts of Interest
The authors declare no conflicts of interests in relation to this work.
- Campo S, Sardo M, Trimarchi G, Bonaiuto M, Fontana L, Castaldo M, Bonaiuto A, Saitta C, Bitto A, Manduca B, Riggio S, Saitta A (2004) Association between serum paraoxonase (PON1) gene promoter T(-107)C polymorphism, PON1 activity and HDL levels in healthy Sicilian octogenarians. Exp Gerontol 39:1089–1094CrossRefGoogle Scholar
- Danzi–Soares NJ, Genta PR, Nerbass FB, Pedrosa RP, Soares FS, César LA, Drager LF, Skomro R, Lorenzi–Filho G (2012) Obstructive sleep apnea is common among patients referred for coronary artery bypass grafting and can be diagnosed by portable monitoring. Coron Artery Dis 23:31–38CrossRefGoogle Scholar
- Gross ER, Ladisa JFJR, Weihrauch D, Olson LE, Kress TT, Hettrick DA, Pagelps WDC, Kersten JR (2003) Reactive oxygen species modulate coronary wall shear stress and endothelial function during hyperglycemia. Am J Phys 284:H1552–H1559Google Scholar
- Lavie L, Vishnevsky A, Lavie P (2003) Evidence for lipid peroxidation in obstructive sleep apnea. Sleep 27:123–128Google Scholar
- Ng CJ, Wadleigh DJ, Gangopadhyay A, Hama S, Grijalva VR, Navab M, Fogelman AM, Reddy ST (2001) Paraoxonase–2 is a ubiquitously expressed protein with antioxidant properties and is capable of preventing cell–mediated oxidative modification of low density lipoprotein. J Biol Chem 276:44444–44449CrossRefGoogle Scholar
- WHO (1999) Diagnosis and classification of diabetes mellitus and its complications. Report of a WHO consultation. Part 1. Diagnosis and classification of diabetes mellitus. Report no. 99. WHO, Geneva, p 2Google Scholar
- Zama T, Murata M, Matsubara Y, Kawano K, Aoki N, Yoshino H, Watanabe G, Ishikawa K, Ikeda Y (1997) A 192arg variant of the human paraoxonase (HUMPONA) gene polymorphism is associated with an increased risk of coronary artery disease in the Japanese. Arterioscler Thromb Vasc Biol 17:3565–3569CrossRefGoogle Scholar