O. Hasselwander et al., Paraoxonase polymorphisms are not associated with cardiovascular risk in renal transplant recipients, KIDNEY INT, 56(1), 1999, pp. 289-298
Background. Paraoxonase (PON1) gene variants have been identified as risk f
actors for cardiovascular disease (CVD). There are two common PON1 polymorp
hisms 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 incr
eased prevalence of conventional risk factors.
Methods. We therefore investigated PON1 polymorphisms in renal transplant r
ecipients (N = 491) with (N = 103) and without CVD (N = 388) using polymera
se chain reaction-restriction fragment length analysis. PON1 polymorphisms
and their associated PON1/arylesterase activities were also assessed in a s
ubgroup of patients (N = 165).
Results. The genotype distribution and allele frequencies for both polymorp
hisms were similar in both groups. The frequencies for LL, LM, and MM genot
ypes for the 55 position in patients with CVD were 0.39, 0.51. and 0.10, re
spectively, 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 positi
on were 0.48. 0.43, and 0.09, respectively, in patients with CVD compared w
ith 0.46, 0.46, and 0.08 in patients without CVD (P = 0.8). There were high
ly 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 PO
N1 gene variants, conferring higher enzyme activity, and the increased card
iovascular risk in renal transplant recipients.