South Asian renal transplant recipients have a higher incidence of cardiovascular disease compared with Caucasian renal transplant recipients. We carried out a study to determine whether paraoxonase 1, a novel biomarker for cardiovascular risk, was decreased in South Asian compared with Caucasian renal transplant recipients. Subjects were matched two to one on the basis of age and sex for a total of 129 subjects. Paraoxonase 1 was measured by mass, arylesterase activity, and two-substrate phenotype assay. Comparisons were made by using a matched design. The frequency of PON1 QQ, QR and RR phenotype was 56%, 37%, and 7% for Caucasian subjects versus 35%, 44%, and 21% for South Asian subjects ( ？ 2 = 7 . 7 2 , ？？ = 0 . 0 2 ). PON1 mass and arylesterase activity were not significantly different between South Asian and Caucasian subjects. PON1 mass was significantly associated with PON1 phenotype ( ？？ = 0 . 0 0 0 1 ), HDL cholesterol ( ？ = 0 . 0 0 9 ), LDL cholesterol ( ？？ = 0 . 0 2 ), and diabetes status ( ？？ < 0 . 0 5 ). Arylesterase activity was only associated with HDL cholesterol ( ？？ = 0 . 0 0 3 ). Thus the frequency of the PON1 RR phenotype was higher and that of the QQ phenotype was lower in South Asian versus Caucasian renal transplant recipients. However, ethnicity was not a significant factor as a determinant of PON1 mass or arylesterase activity, with or without analysis including PON1 phenotype. The two-substrate method for determining PON1 phenotype may be of value for future studies of cardiovascular complications in renal transplant recipients. 1. Introduction Kidney transplant recipients (KTRs) are known to be at increased risk for cardiovascular disease and by three years after transplant about 40% of KTRs have experienced a cardiovascular disease-related event [1]. The incidence of disease is occurring in the context of best medical practice for treatment of established cardiovascular risk factors. Thus there is a need to identify novel risk factors with the objective of improving treatment and reduction of the incidence of cardiovascular disease. End-stage renal disease, the precursor to KTR, is increasing in individuals of South Asian ethnicity relative to subjects of Caucasian ethnicity [1]. There is a need to characterize these subjects and determine whether novel risk factors for cardiovascular disease are present in an ethnicity-dependent manner. The current study was designed to compare two novel risk factors, adiponectin and paraoxonase 1 (PON1), as candidates for differing risk between South Asian and Caucasian KTR. We observed
References
[1]
G. V. Ramesh Prasad, S. K. Vangala, S. A. Silver et al., “South Asian ethnicity as a risk factor for major adverse cardiovascular events after renal transplantation,” Clinical Journal of the American Society of Nephrology, vol. 6, no. 1, pp. 204–211, 2011.
[2]
G. V. Ramesh Prasad, L. Vorobeichik, M. M. Nash et al., “Lower total and percent of high-molecular weight adiponectin concentration in South Asian kidney transplant recipients,” Clinical Kidney Journal, vol. 5, pp. 124–129, 2012.
[3]
P. W. Connelly, B. Zinman, G. F. Maguire et al., “Association of the novel cardiovascular risk factors paraoxonase 1 and cystatin C in type 2 diabetes,” Journal of Lipid Research, vol. 50, no. 6, pp. 1216–1222, 2009.
[4]
P. W. Connelly, G. F. Maguire, C. M. Picardo, J. F. Teiber, and D. Draganov, “Development of an immunoblot assay with infrared fluorescence to quantify paraoxonase 1 in serum and plasma,” Journal of Lipid Research, vol. 49, no. 1, pp. 245–250, 2008.
[5]
R. J. Richter, G. P. Jarvik, and C. E. Furlong, “Paraoxonase 1 (PON1) status and substrate hydrolysis,” Toxicology and Applied Pharmacology, vol. 235, no. 1, pp. 1–9, 2009.
[6]
N. Gupta, S. Singh, V. N. Maturu, Y. P. Sharma, and K. D. Gill, “Paraoxonase 1 (PON1) polymorphisms, haplotypes and activity in predicting CAD risk in North-West Indian Punjabis,” PLoS ONE, vol. 6, no. 5, Article ID e17805, 2011.
[7]
N. Gupta, K. Gill, and S. Singh, “Paraoxonases: structure, gene polymorphism & role in coronary artery disease,” Indian Journal of Medical Research, vol. 130, no. 4, pp. 361–368, 2009.
[8]
M. Rosenblat and M. Aviram, “Paraoxonases role in the prevention of cardiovascular diseases,” BioFactors, vol. 35, no. 1, pp. 98–104, 2009.
[9]
L. P. Précourt, D. Amre, M. C. Denis et al., “The three-gene paraoxonase family: physiologic roles, actions and regulation,” Atherosclerosis, vol. 214, no. 1, pp. 20–36, 2011.
[10]
J. Camps, J. Marsillach, and J. Joven, “Measurement of serum paraoxonase-1 activity in the evaluation of liver function,” World Journal of Gastroenterology, vol. 15, no. 16, pp. 1929–1933, 2009.
[11]
J. Kannampuzha, P. B. Darling, G. F. Maguire et al., “Paraoxonase 1 arylesterase activity and mass are reduced and inversely related to C-reactive protein in patients on either standard or home nocturnal hemodialysis,” Clinical Nephrology, vol. 73, no. 2, pp. 131–138, 2010.
[12]
A. Gugliucci, E. Kinugasa, K. Kotani, R. Caccavello, and S. Kimura, “Serum paraoxonase 1 (PON1) lactonase activity is lower in end-stage renal disease patients than in healthy control subjects and increases after hemodialysis,” Clinical Chemistry and Laboratory Medicine, vol. 49, no. 1, pp. 61–67, 2011.
[13]
O. Gungor, F. Kircelli, M. S. Demirci, et al., “Serum paraoxonase 1 activity predicts arterial stiffness in renal transplant recipients,” Journal of Atherosclerosis and Thrombosis, vol. 18, no. 10, pp. 901–905, 2011.
[14]
K. D. Navab, O. Elboudwarej, M. Gharif, et al., “Chronic inflammatory disorders and accelerated atherosclerosis: chronic kidney disease,” Current Pharmaceutical Design, vol. 17, pp. 17–20, 2011.
[15]
N. D. Vaziri, K. Navab, P. Gollapudi, et al., “Salutary effects of hemodialysis on low-density lipoprotein proinflammatory and high-density lipoprotein anti-inflammatory properties in patient with end-stage renal disease,” National Medical Association, vol. 103, pp. 524–533, 2011.
[16]
G. P. Jarvik, T. S. Hatsukami, C. Carlson et al., “Paraoxonase activity, but not haplotype utilizing the linkage disequilibrium structure, predicts vascular disease,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 23, no. 8, pp. 1465–1471, 2003.
[17]
G. Paragh, I. Seres, M. Harangi et al., “Discordance in human paraoxonase-1 gene between phenotypes and genotypes in chronic kidney disease,” Nephron - Clinical Practice, vol. 113, no. 1, pp. c46–c53, 2009.
[18]
G. Paragh, L. Asztalos, I. Seres et al., “Serum paraoxonase activity changes in uremic and kidney-transplanted patients,” Nephron, vol. 83, no. 2, pp. 126–131, 1999.
[19]
S. Bhaskar, M. Ganesan, G. R. Chandak et al., “Association of PON1 and APOA5 gene polymorphisms in a cohort of indian patients having coronary artery disease with and without type 2 diabetes,” Genetic Testing and Molecular Biomarkers, vol. 15, no. 7-8, pp. 507–512, 2011.
[20]
M. Boemi, I. Leviev, C. Sirolla, C. Pieri, M. Marra, and R. W. James, “Serum paraoxonase is reduced in type 1 diabetic patients compared to non-diabetic, first degree relatives; influence on the ability of HDL to protect LDL from oxidation,” Atherosclerosis, vol. 155, no. 1, pp. 229–235, 2001.
[21]
J. Ruiz, H. Blanche, R. W. James et al., “Gln-Arg192 polymorphism of paraoxonase and coronary heart disease in type 2 diabetes,” Lancet, vol. 346, no. 8979, pp. 869–872, 1995.
[22]
Y. Ikeda, T. Suehiro, T. Itahara et al., “Human serum paraoxonase concentration predicts cardiovascular mortality in hemodialysis patients,” Clinical Nephrology, vol. 67, no. 6, pp. 358–365, 2007.
[23]
O. Hasselwander, D. A. Savage, D. Mcmaster et al., “Paraoxonase polymorphisms are not associated with cardiovascular risk in renal transplant recipients,” Kidney International, vol. 56, no. 1, pp. 289–298, 1999.
