Apolipoprotein E controls the risk and age at onset of Parkinson disease.
(Journal Article;Multicenter Study)
BACKGROUND: Similarities between Alzheimer disease (AD) and Parkinson disease (PD) suggest a possible role for apolipoprotein E (APOE) in PD. Most previous studies seeking to establish such a link used case-control datasets and results have been inconsistent. OBJECTIVE: To investigate APOE's role in PD using family-based association analyses. METHODS: APOE functional polymorphisms were genotyped for 658 PD affected families, including 282 multiplex and 376 singleton families. The pedigree disequilibrium test (PDT) and the genotype-PDT were used to test the risk effect of APOE. The Monks-Kaplan test was used to evaluate the effect of APOE on age at onset of PD. RESULTS: APOE was significantly associated with risk of developing PD. Stratified analysis revealed that APOE was most strongly associated with families with a positive PD family history (global p = 0.003). Like AD, the APOE-4 allele increases disease risk while the APOE-3 allele decreases risk. We detected a positive association of APOE-3 (p = 0.019) and a negative association of APOE-4 (p = 0.015) with age at onset in PD. CONCLUSIONS: The APOE-4 allele increases risk and decreases age at onset of PD, an association that may not be dependent upon cognitive impairment.
Li, YJ; Hauser, MA; Scott, WK; Martin, ER; Booze, MW; Qin, XJ; Walter, JW; Nance, MA; Hubble, JP; Koller, WC; Pahwa, R; Stern, MB; Hiner, BC; Jankovic, J; Goetz, CG; Small, GW; Mastaglia, F; Haines, JL; Pericak-Vance, MA; Vance, JM
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