Paraoxonase polymorphisms are not associated with cardiovascular risk in renal transplant recipients

被引:77
作者
Hasselwander, O
Savage, DA
McMaster, D
Loughrey, CM
McNamee, PT
Middleton, D
Nicholls, DP
Maxwell, AP
Young, IS
机构
[1] Queens Univ Belfast, Sch Clin Med, Belfast BT7 1NN, Antrim, North Ireland
[2] Royal Grp Hosp, Dept Clin Biochem, Belfast, Antrim, North Ireland
[3] Belfast City Hosp, Reg Nephrol Unit, Belfast, Antrim, North Ireland
[4] No Ireland Tissue Typing Serv, Belfast, Antrim, North Ireland
关键词
transplantation; PON1; polymorphisms; genotypes; enzyme activity; cardiovascular disease; diabetes;
D O I
10.1046/j.1523-1755.1999.00521.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background. Paraoxonase (PON1) gene variants have been identified as risk factors for cardiovascular disease (CVD). There are two common PON1 polymorphisms at position 55 (Leu-Met change) and 192 (Gln-Arg change) of the amino acid chain. Leucine at position 55 and arginine at position 192 have been associated with increased cardiovascular risk. The increased prevalence of CVD in renal transplant recipients can be only partly explained by the increased prevalence of conventional risk factors. Methods. We therefore investigated PON1 polymorphisms in renal transplant recipients (N = 491) with (N = 103) and without CVD (N = 388) using polymerase chain reaction-restriction fragment length analysis. PON1 polymorphisms and their associated PON1/arylesterase activities were also assessed in a subgroup of patients (N = 165). Results. The genotype distribution and allele frequencies for both polymorphisms were similar in both groups. The frequencies for LL, LM, and MM genotypes for the 55 position in patients with CVD were 0.39, 0.51. and 0.10, respectively, compared with 0.43, 0.43, and 0.14 in patients without CVD (P = 0.31). The distribution for the QQ, QR, and RR genotypes at the 192 position were 0.48. 0.43, and 0.09, respectively, in patients with CVD compared with 0.46, 0.46, and 0.08 in patients without CVD (P = 0.8). There were highly significant differences in serum activities of PON1/arylesterase between genotypes defined by 55 and 192 polymorphisms. Leucine at position 55 and arginine at position 192 were associated with higher activities. Conclusion. These data indicate that there is no association between the PON1 gene variants, conferring higher enzyme activity, and the increased cardiovascular risk in renal transplant recipients.
引用
收藏
页码:289 / 298
页数:10
相关论文
共 49 条
[1]   SERUM PARAOXONASE ACTIVITY, CONCENTRATION, AND PHENOTYPE DISTRIBUTION IN DIABETES-MELLITUS AND ITS RELATIONSHIP TO SERUM-LIPIDS AND LIPOPROTEINS [J].
ABBOTT, CA ;
MACKNESS, MI ;
KUMAR, S ;
BOULTON, AJ ;
DURRINGTON, PN .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1995, 15 (11) :1812-1818
[2]  
ADKINS S, 1993, AM J HUM GENET, V52, P598
[3]   The Gln-Arg191 polymorphism of the human paraoxonase gene (HUMPONA) is not associated with the risk of coronary artery disease in Finns [J].
Antikainen, M ;
Murtomaki, S ;
Syvanne, M ;
Pahlman, R ;
Tahvanainen, E ;
Jauhiainen, M ;
Frick, MH ;
Ehnholm, C .
JOURNAL OF CLINICAL INVESTIGATION, 1996, 98 (04) :883-885
[4]  
Blatter Garin Marie-Claude, 1997, Journal of Clinical Investigation, V99, P62
[5]   LONG-TERM COMPLICATIONS OF RENAL-TRANSPLANTATION [J].
BRAUN, WE .
KIDNEY INTERNATIONAL, 1990, 37 (05) :1363-1378
[6]   The effect of the human serum paraoxonase polymorphism is reversed with diazoxon, soman and sarin [J].
Davies, HG ;
Richter, RJ ;
Keifer, M ;
Broomfield, CA ;
Sowalla, J ;
Furlong, CE .
NATURE GENETICS, 1996, 14 (03) :334-336
[7]  
ECKERSON HW, 1983, AM J HUM GENET, V35, P214
[8]  
FRIEDEWALD WT, 1972, CLIN CHEM, V18, P499
[9]   PURIFICATION OF RABBIT AND HUMAN SERUM PARAOXONASE [J].
FURLONG, CE ;
RICHTER, RJ ;
CHAPLINE, C ;
CRABB, JW .
BIOCHEMISTRY, 1991, 30 (42) :10133-10140
[10]  
GAN KN, 1991, DRUG METAB DISPOS, V19, P100