Age at onset of Parkinson disease and apolipoprotein E genotypes

Abstract

Several lines of evidence suggest that the variable age at onset of Parkinson disease (PD) is likely influenced by genes. The apolipoprotein E (APOE) gene is associated with onset of Alzheimer disease, and possibly other neurodegenerative disorders. APOE has been investigated in relation to onset of PD, but results have been inconsistent. The aim of the present study was to determine if APOE genotypes are associated with onset age of PD, using a patient population large enough to assure sufficient power. We studied 521 unrelated Caucasian patients with idiopathic PD from movement disorder clinics in Oregon and Washington. Genotyping and statistical analyses were carried out using standard methods. Age at onset of PD was significantly earlier in patients with the varepsilon3varepsilon4/varepsilon4varepsilon4 genotype than in patients with the varepsilon3varepsilon3 genotype (56.1 +/- 10.9 vs. 59.6 +/- 11.0, P = 0.003). The significantly earlier onset of PD was not influenced by the possible effects of recruitment site, family history and gender. The effect of the varepsilon2varepsilon3 genotype on onset of PD differed between the two recruitment sites. There was a trend for earlier onset of PD in varepsilon2varepsilon3 patients than in varepsilon3varepsilon3 patients only in the Oregon sample. In conclusion, APOE is associated with age at onset of PD.

Association of APOE with age at onset of sporadic amyotrophic lateral sclerosis

“…The association of APOE ε4 with earlier age at onset of ALS without SOD1 gene mutations suggests that an impaired brain regenerative capacity conferred by the ε4 allele may interact with ALS-causing genetic and/or environmental factors to make the disease present earlier, although there is no detectable influence of APOE variants on disease risk. Similar findings have been reported in PD and Pick's disease [21,22]. Moreover, much of the association of APOE ε4 with sporadic, but not necessarily familial, AD is caused by the earlier age at onset in ε4 carriers [23][24][25].…”

Visualizing disease associations: graphic analysis of frequency distributions as a function of age using moving average plots (MAP) with application to Alzheimer's and Parkinson's disease

“…Average age at onset was 2.2 years earlier in ε4-carriers than non-ε4-carriers (56.6 ± 12.3 vs. 58.8 ± 12.1, p=0.0002). A modest but significant association between ε4 and age at onset of PD has been noted previously [Pankratz et al, 2006; Zareparsi et al, 2002]. …”

Apolipoprotein E controls the risk and age at onset of Parkinson disease

“…13 However, a later study using a relatively large sample size (521 unrelated Caucasian PD patients) showed that individuals with APOE-34 or APOE-44 genotypes, not APOE-23 carriers, have significantly earlier AAO than those with the APOE-33 genotype. 14 Significant association has also been found between the APOE-4 allele and PD patients with dementia. 11 Finally, the APOE-24 genotype was shown to associate with PD in a small Chinese sample (69 PD cases and 160 controls).…”