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


CONCLUSIONS
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.
School of Clinical Medicine, The Queen's University of Belfast, Northern Ireland.
O
O
Hasselwander
D A
DA
Savage
D
D
McMaster
C M
CM
Loughrey
P T
PT
McNamee
D
D
Middleton
D P
DP
Nicholls
A P
AP
Maxwell
I S
IS
Young
D000328:Adult; D000483:Alleles; D000595:Amino Acid Sequence / Q000235:genetics; D043303:Aryldialkylphosphatase; D002265:Carboxylic Ester Hydrolases / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000235:genetics*; D004950:Esterases / Q000097:blood / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000502:physiology*; D012150:Polymorphism, Restriction Fragment Length; D011183:Postoperative Complications; D012307:Risk Factors
D004950:Esterases; D002265:Carboxylic Ester Hydrolases; C019734:arylesterase; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human