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Environmental and genetic risk factors for susceptibility and progression in Parkinson's disease.

紀錄類型:	書目-電子資源 : Monograph/item
書名/作者:	Environmental and genetic risk factors for susceptibility and progression in Parkinson's disease.
作者:	Paul, Kimberly Carol.
出版者:	Ann Arbor : : ProQuest Dissertations & Theses, , 2016
面頁冊數:	100 p.
附註:	Source: Dissertation Abstracts International, Volume: 77-10(E), Section: B.
Contained By:	Dissertation Abstracts International77-10B(E).
標題:	Epidemiology.
ISBN:	9781339736945
摘要、提要註:	Parkinson's disease (PD) is one of the most common neurodegenerative disorders and has a complex multifactorial etiology, likely involving not only exposure to environmental toxins but also an underlying genetic susceptibility. Several major molecular pathways are implicated in PD pathogenesis; many, including impaired ubiquitin-proteasome system, mitochondrial dysfunction, and neuroinflammation, involve oxidative stress as an underlying mechanism. Further, the course and severity of symptom progression is highly variable, and oxidative stress related pathways may be involved in symptom progression.

Environmental and genetic risk factors for susceptibility and progression in Parkinson's disease.
Paul, Kimberly Carol.

Environmental and genetic risk factors for susceptibility and progression in Parkinson's disease. - Ann Arbor : ProQuest Dissertations & Theses, 2016 - 100 p.

Source: Dissertation Abstracts International, Volume: 77-10(E), Section: B.

Thesis (Ph.D.)--University of California, Los Angeles, 2016.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders and has a complex multifactorial etiology, likely involving not only exposure to environmental toxins but also an underlying genetic susceptibility. Several major molecular pathways are implicated in PD pathogenesis; many, including impaired ubiquitin-proteasome system, mitochondrial dysfunction, and neuroinflammation, involve oxidative stress as an underlying mechanism. Further, the course and severity of symptom progression is highly variable, and oxidative stress related pathways may be involved in symptom progression.

ISBN: 9781339736945Subjects--Topical Terms:

342217
Epidemiology.

Environmental and genetic risk factors for susceptibility and progression in Parkinson's disease.
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245 1 0 $a Environmental and genetic risk factors for susceptibility and progression in Parkinson's disease.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2016
300 $a 100 p.
500 $a Source: Dissertation Abstracts International, Volume: 77-10(E), Section: B.
500 $a Adviser: Beate R. Ritz.
502 $a Thesis (Ph.D.)--University of California, Los Angeles, 2016.
520 $a Parkinson's disease (PD) is one of the most common neurodegenerative disorders and has a complex multifactorial etiology, likely involving not only exposure to environmental toxins but also an underlying genetic susceptibility. Several major molecular pathways are implicated in PD pathogenesis; many, including impaired ubiquitin-proteasome system, mitochondrial dysfunction, and neuroinflammation, involve oxidative stress as an underlying mechanism. Further, the course and severity of symptom progression is highly variable, and oxidative stress related pathways may be involved in symptom progression.
520 $a Widely used organophosphate (OP) pesticides can induce oxidative stress and are reported to increase PD risk, and may be involved in symptom progression. Additionally, two single nucleotide polymorphisms (SNPs) from the PON1 gene influence the ability to metabolize OPs. Nitric oxide synthase (NOS) genes are candidates for PD because NOS enzymes produce nitric oxide (NO), a pro-oxidant that can damage neurons. The NFE2L2 and PPARGC1alpha genes encode for important transcription factors that activate multiple antioxidant defense mechanisms in response to oxidative stress.
520 $a In the Parkinson's Environment and Gene (PEG) case control study, we investigated 8 NOS SNPs and interactions with both household and ambient agricultural OP exposures assessed with geographic information system (GIS) and PD susceptibility with logistic regression models. In the patient only cohort, we employed repeated-measures regression to assess associations between ambient OP exposure and/or PON1 L55M genotypes and symptom progression. And finally, we investigated the influence of haplotypes for NFE2L2 and PPARGC1alpha and their interactions with exposures to the pesticides maneb and paraquat (MB/PQ) on PD occurrence (using logistic regression models) and also on progression of motor symptoms and cognitive decline in patients followed prospectively (repeated measures models).
520 $a In comparing PD in homozygous variant carriers of NOS2A rs1060826 versus homozygous wildtype or heterozygotes, we estimate an adjusted OR of 1.51 (95% CI=0.95, 2.41). When considering interactions between NOS1 rs2682826 and OP exposure from household use, the OR for frequent OP use alone 1.30 (95% CI=0.72, 2.34) and for the CT+TT genotype alone 0.89 (95% CI= 0.58, 1.39), and frequent OP use combined with the CT+TT genotype was 2.84 (95% CI=1.49, 5.40) (interaction p-value 0.04). Similar results were seen for ambient OP exposure. Interactions between OP exposure and 3 other NOS1 SNPs and a genetic risk score combining all NOS1 SNPs reached statistical significance.
520 $a High OP exposures were associated with faster progression of both motor (UPDRS=0.002) and cognitive scores (MMSE p=0.008). The PON1 55MM genotype was associated with worse cognitive scores and faster progression of motor (UPDRS=0.01) and depressive symptoms (GDS p=0.008). We also found the PON1 L55M variant to interact with OP exposures in influencing MMSE cognitive scores (p=0.02).
520 $a Two NFE2L2 haplotypes were associated with significant increases in the risk of developing PD (p<0.04) and with faster cognitive decline (MMSE p<0.0006). None of the PPARGC1alpha haplotypes were marginally associated with PD risk. However, one haplotype interacted with MB/PQ exposure (p=0.03), such that highly exposed haplotype carriers showed no increased risk of PD while these pesticides increased PD risk in wildtype haplotype carriers. Additionally, three PPARGC1alpha haplotypes were associated with differing rates of motor symptom progression.
520 $a The observations are consistent with the hypothesis that oxidative stress-inducing mechanisms influence PD risk and progression.
590 $a School code: 0031.
650 4 $a Epidemiology. $3 342217
690 $a 0766
710 2 0 $a University of California, Los Angeles. $b Epidemiology. $3 686730
773 0 $t Dissertation Abstracts International $g 77-10B(E).
790 $a 0031
791 $a Ph.D.
792 $a 2016
793 $a English