Apolipoprotein E genotypes and age at onset of Parkinson's disease

Fuente‐Fernández, Raúl de la; Sellers, A.; Beyer, Katrin; Lao, José I.

doi:10.1002/ana.410440231

Cited by 8 publications

(9 citation statements)

References 3 publications

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“…Other contributors may be differences in ethnic origin, proportion of familial cases and other differences between sites. The majority of the subjects in this study were of Northern European origin, whereas the subjects in two studies were Spanish [de la Fuente-Fernandez et al, 1998] and Italian [Oliveri et al, 1999]. It is possible that the effect of APOE on onset of PD differs among ethnic groups, just as the effect of APOE on AD differs among ethnic groups [Farrer et al, 1997].…”

Section: Discussionmentioning

confidence: 86%

“…Subsequently, four studies have examined the effect of APOE alleles on age at onset of PD. One study found a non-signi®cant 1.6 year earlier onset in e4-carriers ], whereas three studies did not detect an earlier onset in e4-carriers [de la Fuente-Fernandez et al, 1998;Oliveri et al, 1999;Maraganore et al, 2000]. Interestingly, one study found evidence for signi®cantly earlier age at onset in e2e3 patients compared to e3e3 patients [Maraganore et al, 2000].…”

Section: Introductionmentioning

confidence: 90%

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Age at onset of Parkinson disease and apolipoprotein E genotypes

et al. 2001

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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.

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Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 90%

Age at onset of Parkinson disease and apolipoprotein E genotypes

et al. 2001

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“…Interestingly, in the cohort by Zareparsi et al [2002], 29% of the patients had positive FH, while the proportion of patients with positive FH was 12% and 15% in two of the previous studies [Inzelberg et al, 1998;de la Fuente-Fernandez et al, 1998]. In addition, the authors excluded patients whose age of onset was 30 or less, to avoid the inclusion of patients with parkin mutations.…”

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confidence: 98%

“…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.…”

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confidence: 99%

Onset age of Parkinson disease

2002

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“…12 Thus far, ApoE analyses in PD, however, have remained contradictory. [13][14][15][16][17][18] Here, we studied several polymorphisms of the ␣-SYN gene locus and the ApoE gene independently and in a combined analysis to define susceptibility genotypes for PD.…”

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confidence: 99%

Increased susceptibility to sporadic Parkinson's disease by a certain combined ?-synuclein/apolipoprotein E genotype

et al. 1999

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Parkinson's disease (PD) is one of the most common neurodegenerative disorders affecting about 1% of Western populations older than age 50. The pathological hallmark of PD are Lewy bodies, that is, intracytoplasmic inclusion bodies in affected neurons of the substantia nigra. Recently, α‐synuclein (α‐SYN) has been identified as the main component of Lewy bodies in sporadic PD, suggesting involvement in neurodegeneration via protein accumulation. The partially overlapping pathology of PD and Alzheimer's disease, as well as striking structural similarities of α‐SYN and apolipoprotein E, which is a major risk factor for late‐onset Alzheimer's disease, prompted us to investigate the influence of different α‐SYN and apolipoprotein E alleles for developing sporadic PD. We performed association studies in 193 German PD patients and 200 healthy control subjects matched for age, sex, and origin. A polymorphism in the promoter region of the α‐SYN gene (NACP‐Rep1) as well as of the closely linked DNA markers D4S1647 and D4S1628 revealed significant differences in the allelic distributions between PD patients and the control group. Furthermore, the Apoε4 allele but not the Th1/E47 promoter polymorphism of the apolipoprotein E gene was significantly more frequent among early‐onset PD patients (age at onset, <50 years) than in late‐onset PD. Regarding the combination of the Apoε4 allele and allele 1 of the α‐SYN promoter polymorphism, a highly significant difference between the group of PD patients and control individuals has been found, suggesting interactions or combined actions of these proteins in the pathogenesis of sporadic PD. PD patients harboring this genotype have a 12.8‐fold increased relative risk for developing PD during their lives. Ann Neurol 1999;45:611–617

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Apolipoprotein E genotypes and age at onset of Parkinson's disease

Abstract: We read with interest the article by Zareparsi and colleagues.' The authors analyzed the influence of the apolipoprotein E (ApoE) ~4 allele on the age at onset of Parkin-

Cited by 8 publications

References 3 publications

Age at onset of Parkinson disease and apolipoprotein E genotypes

Age at onset of Parkinson disease and apolipoprotein E genotypes

Onset age of Parkinson disease

Increased susceptibility to sporadic Parkinson's disease by a certain combined ?-synuclein/apolipoprotein E genotype

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