We have read with interest the article entitled ''Age of onset of Parkinson disease and apolipoprotein E genotypes'' by Zareparsi et al. [2002]. The authors tested the influence of ApoE genotype on the age of onset of Parkinson disease (PD). They found that the presence of the e4 allele is accompanied by younger age of onset, after adjusting for family history (FH).
We have previously studied consecutive PD patients and compared the ages of onset of e4 carriers and those who were not e4 carriers. The age of onset was 67.1 AE 10.4 years among e4 carriers versus 68.7 AE 11.6 years among non-e4 carriers (P > 0.1) [Inzelberg et al., 1998]. Thus, our findings do not replicate those of Zareparsi et al. [2002] concerning the influence of ApoE genotypes on the age of onset. Other authors have also reported this lack of relationship between the e4 allele and the age of onset in PD. Zareparsi et al. [2002] summarized in their Table IV previous studies focusing on the age of onset of PD and ApoE genotypes. One of these studies, by de la Fuente-Fernandez et al. [1998], found in fact, paradoxically, significantly older ages of PD onset in e4 carriers. Because all studies [de la Fuente-Fernandez et al., 1998;Inzelberg et al., 1998;Oliveri et al., 1999] cited in Table IV of Zareparsi et al. [2002] tested the same hypothesis concerning the effect of ApoE genotype on the age of onset, their combined P value could be calculated using Fisher's inverse w 2 method of combined independent tests on the same hypothesis [Hedges and Olkin, 1985]. The P value for the combination of the additional studies cited in Table IV was 0.598, thus ages of onset were not significantly different among e4 carriers and those who were not. One possible explanation for this discrepancy could be the size of the samples, which were not large enough in each of these studies, as suggested by Zareparsi et al. [2002]. The authors calculated the required number of patients needed to reach a power of 80%. The combination of the studies cited in Table IV, which we have used in our calculation of combined P value, provided the necessary number of patients to demonstrate the possible effect of ApoE genotypes on an age of onset difference of four years, if such a difference had existed. Still, the P value