Genes
that have been associated with Parkinson's disease RSS
feeds link to Pubmed
GWAS
from Genome.gov
AAK1 ACMSD ATF6 BMP4 BRDG1 BST1 C10orf32 C17orf69 ISM1 (c20orf82) CCDC62
CNNM2 CYP17A1 DBC1 DGKQ DLG2 DSG3 EIF4G1 GAK GBA HIP1R HLA-DRB5 IMP5
ITGA8 KIAA1267 LAMP3 LOC644246 MAPT MCCC1 MMRN1 NSF NUCKS1 OCA2 PARK16
PLEKHM1 PM20D1 PRRG4 QSER1 RAB7L1 RAI1 RIT2 SCARB2 SEMA5A SLC41A1 SNCA
SREBF1 STBD1 STK39 SYT11 SYT4 TAS1R2 UNC13B USP25 WNT3
Pre GWAS and others: Data from various sources including Pubmed alerts
A
B
and : PDGene developed by the Max
Planck Institute for molecular genetics, Berlin; The
Michael J Fox foundation , and the Alzheimer
Research forum See also The
Genetic Association database at NIH ... Genotator
at Harvard University and HUGE
navigator See also PDBase
The
Parkinson Disease Mutation Database Leiden
Open Variation Database ..Mutation
database for Parkinson's disease
Copy
number variations
Parkinson's
epistasis
MicroRNA's implicated in Parkinson's disease
Need KEGG mapping: CHRNA5
DNAJC6
SIRT1
LAMP2
HLA-DRB1
. ATG7
. HER2
SMPD1
ATP6AP2
(mutation) FBXO7
S100B.
NOD2
HLA-DQA1
AGER
. SHMT
CHRNB3
LAMP3
ESR1
S1PR1
OLFM3
LRPAP1
PGLYRP2
PGLYRP3
PGLYRP4
NCAPD2
STX1B
TLR9
TLR2
TLR4
CHCHD2
MC1R
ALDH2
. CHRNA4
TMEM230
Viral and other infections Wikipedia and Reference
- Encephalitis
Lethargica possibly related to the 1918 flu
pandemic Treatment of these patients with L-DOPA,
recorded in the film Awakenings
helped to revolutionise Parkinson's disease therapy Foley
2009
- An enterovirus , as well as the poliovirus and coxsackievirus
B have been linked to this condition (electron-microscope study
of archived post-mortem tissue) Dourmashkin
et al, 2012 and 2018
- Influenza infection has been related to Substantia nigra cell loss
in Man Mihara
et al, 2001
- Influenza H1N1 infection in mice targets the Substantia nigra and
kills dopamine neurones Jang
et al, 2009
- The influenza virus has been recorded in the substantia nigra
of Parkinson's disease brains Rohn
and Catlin, 2011
- The Epstein-Barr virus can cause post-encephalitic Parkinsonism
Espay
and Henderson, 2011
- CSF antibodies to coronavirus
have been observed in some patients Fazzini
et al, 1992
- Post-mortem brain viral DNA
- HSV-1: Control 25%: PD 17.5% .
- HHV-6: Control 87.5% PD 75%
- Varicella: Control 27.5% PD 40% Hemling
et al, 2003
- Hepatitis C infection associated with Parkinson's disease: Viral
infection caused dopaminergic neuronal death in the midbrain neuron-glia
coculture system in rats Wu
et al, 2015 Tsai
et al, 2015
- Hepatitis B and Hepatitis C infection associated with Parkinson's
disease Pakpoor
et al, 2017
- Hepatitis C infection associated with Parkinson's disease risk (meta-analysis)
Wijarnpreecha
et al, 2018
- Serum and CSF antibodies: Herpes simplex virus 1 , measles, and
rubella antibody titres were lower in sera of PD patients: Serum influenza
antibody titres were higher in post-encephalitic Parkinsonism Elizan
et al, 1979
- Association with Japanese B encephalitis virus Das
et al, 2011
- The incidence of Parkinson's disease, as well as that of many other
disorders has been reported to be increased in poliomyelitis survivors
Kang
and Lin, 2011
- Mumps, influenza , whooping cough and herpes simplex infections
have been associated with Parkinson;s disease (adjusted by occupation
and family history )Vlajinac
et al, 2012 In a further study Parkinson's disease was significantly
related to mumps [odds ratio adjusted on occupation and family history
of PD (aOR) = 7.86, 95% confidence interval (CI) = 3.77-16.36], scarlet
fever (aOR = 12.18, 95% CI = 1.97-75.19), influenza (aOR = 8.01, 95%
CI = 4.61-13.92), whooping cough (aOR = 19.90, 95% CI = 2.07-190.66)
and herpes simplex infections (aOR = 11.52, 95% CI = 2.25-58.89).
Tuberculosis, measles and chicken pox were not associated with PD
Vlajinac
et al, 2013
- Childhood measles has been inversely associated with Parkinson's
disease Harris
et al, 2012
- The Borna virus has been implicated in Parkinson's disease Zhang
et al, 2013
- No association with Arbovirus
antibodies
Elizan et al, 1978
- A possible association with Toxoplasma
Gondii has been reported in Turkey
Miman et al, 2010
- Transient Parkinsonism has been observed in West Nile virus encephalitis
Robinson
et al, 2003 Dopaminergic drugs inhibit West Nile virus replication
in cell culture
Blazquez et al, 2016
- An increased incidence of Parkinson's disease has been observed
following a whooping cough epidemic (Bordetella pertussis)
de Pedro-Cuesta et al, 1996
- Nocardia asteroides infects many old people and has been implicated
in Parkinson's disease Kohbata
et al, 1993. Infection with this bacterium in mice kills Substantia
nigra neurones Tam
et al, 2002
- formyl-methionyl-leucyl-phenylalanine , also a bacterial product
kills dopamine neurones Gao
et al, 2008
- Helicobacter
pylori seropositivity has been associated with Parkinson's disease
Charlett
et al, 1999
- Helicobacter Suis observed at greater frequency in Parkinson's disease
patients Blaecher
et al, 2013
- Increased dental loss associated with increased cariogenic bacteria
Einarsdóttir
et al, 2009
- Abnormal oral colonisation by gram-negative bacteria (Escherichia
coli , Klebsiella, Kluyvera , Serratia , Proteus and Enterobacter
species) Gosney
et al, 2003
- Increased Staphylococcus aureus in conjunctival flora Kusbeci
et al, 2009
- A case of Parkinson's disease secondary to neurosyphilis Spitz
et al, 2008
- Reduced risk associated with childhood viral infection particularly
measles
Sasco
et al, 1985
- Increased antibody response to Herpes simplex in Parkinson's disease
patients Martilla
and Rinne, 1981
- Case report of Parkinsonism produced by gram-negative sepsis Alasia
et al, 2006
- Case report of Parkinsonism associated with cryptococcal abscesses
of the basal ganglia Camargos
et al, 2006
- Parkinsonism asociated with streptococcal infection McKee
and Sussman, 2005
- A mild form of acute Parkinson's disease has been observed after
a wasp sting Leopold
et al, 1999
- Chronic polysystemic candidiasis produces acetaldehyde, which upon
reaction with dopamine can produce the neurotoxin Salsalinol Epp
and Mravec 2006
- Infectious burden consisting of cytomegalovirus , Epstein-Barr virus
, herpes simplex (HSV-1), B. burgdorferi, C. pneumoniae and H. pylori
is associated with PD Bu
et al, 2015
- Alpha-synuclein restricts brain viral infection (West Nile virus
and Venezuelan equine encephalitis virus) in mice Beatman
et al, 2015. alpha-synuclein also has antimicrobial properties
against bacteria (Escherichia coli and Staphylococcus aureus)and fungi
( Aspergillus flavus, Aspergillus fumigatus and Rhizoctonia solani)
Park
et al, 2016
Chemicals implicated in Parkinson's disease
- MPTP
causes Parkinsonism Langston
et al, 1983
- Paraquat
and rotenone
have been implicated as environmental toxins MPTP, Rotenone and paraquat
all block the mitochondrial
respiratory chain, although there are differences in precise mechanismsArif
and Khan, 2010
- The effects of paraquat on dopaminergic neurones in mice are
attenuated by intergeron gamma ( IFNG ) knockout Mangano
et al, 2011 , as are those of MPTP : IFNG also kills dopamine
neurones, but only in the presence of microglia Mount
et al 2007
- Vitamin K2 has been reported to reverse mitochondrial deficits
in PINK1 deficient Drosophila Vos
et al, 2012
- Lipopolysaccharide intracerebral injection causes Parkinsonism like
effects and dopaminergic damage in rodents Castaño
et al, 1998 (LPS is a component of many bacteria)
- Ammonium chloride and tunicamycin kill dopamine neurones (in fish)
Matsui
et al, 2010
- Exposure to pesticides has been associated with Parkinson's disease
Hatcher
et al, 2008
- PD incidence associated with exposure to certain pesticide ingredients
such as alachlor and broxomy in Nebraska Wan
and Lin, 2016
- Milk intake is associated with substantia nigra neuronal loss in
post-mortem brains unaffected by Parkinson's disease. Residues of
heptachlor epoxide found in 9 of 10 brains in those with high milk
consumption Abbott
et al, 2016
- Household orgabophospate pesticide use associated with an increased
risk of Parkinson's disease Narayan
et al, 2013
- For every 1.0 µg/L of pesticide in groundwater, the risk of
PD increases by 3% (well water samples with atrazine, simazine, alachlor,
and metolachlor measurements) James
and Hall, 2015
- B4GALNT1 (beta-1,4-N-acetyl-galactosaminyl transferase 1 ) knockdown
produces parkinsonism in mice (synthesises ganglosides) Kegg
pathway .Wu
et al, 2011
- Elevated serum levels of the organochlorine pesticide ß-hexachlorocyclohexane
have been reported in Parkinsonian patients Richardson
et al, 2011
- Trichloroethylene inhibits mitochondrial respiration and has been
implicated in Parkinson's disease
Gash et al, 2008: perchloroethylene and carbon tetrachloride tended
toward significance as risk factors Goldman
et al, 2012
- Polychlorinated biphenyls have been linked to Parkinson's disease
pathology, particularly in females Hatcher-Martin
et al, 2012.
- Pesticides
and Parkinson's disease database
- TEMPEST
: A Task Exposure Matrix for Pesticides : Various studies
- The consumption of whalemeat and blubber (probably a concentration
of food chain toxins) has been linked to Parkinson's disease: beta-hexachlorocyclohexane
was also linked to increased risk Petersen
et al, 2008
- BMAA
( beta-Methylamino-L-alanine ), a toxin derived from Cycad seeds causes
a degenerative disease with Parkinsonian features in Guam Vyas
and Weiss, 2009 . BMAA can also be produced by cyanobacteria Cox
et al, 2003
- Methamphetamine use has been implicated as a risk factor Callaghan
et al, 2010
- A metabolite from S.
venezuelae kills dopaminergic neurones in nematodes and in mammalian
SH-SY5Y
cells Caldwell
et al, 2009
- Organophosphate pesticides have been linked to Parkinson's disease
Das
et al, 2011 Wang
et al, 2014
- Fungal-derived 1-octen-3-ol (mushroom
alcohol) causes dopaminergic neurodegeneration in Drosophila Inamdar
et al, 2013
- 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]Pyridine, a byproduct of
cooked meat, is toxic to dopaminergic neurones Griggs
et al, 2014
- Exposure to extremely low frequency magnetic fields associated with
PD Brouwer
et al, 2015
Metals and Parkinson's disease
- Previous exposure to manganese
has been associated with increased risk Park
et al, 2005
- Urban Parkinson disease incidence is higher in US counties with
high industrial release of copper or manganese Willis
et al, 2010
- A significant correlation between blood manganese and signal intensity
in T1-weighted MRI images has been reported in liver-disease patients
with Parkinson-like signs Hudnell,
1999
- Cumulative lead exposure has been associated with Parkinson's disease
Weisskopf
et al, 2010
- Significantly lower levels of Cobalt, Chromium, Iron, Lead, Silicon
and Tin were observed in the CSF of PD patients compared with those
in controls, with a percentage depletion of up to 50% for Chromium
and Lead Alimonti
et al, 2007.
- Decreased Aluminium , Sulphur, Iron and zinc plasma concentrations:
Increased potassium, Magnesium and Copper concentrations Hegde
et al, 2004
- Increased serum iron levels causally associated with a decreased
risk of developing PD Pichler
et al, 2013.
- Aluminium, copper, iron, manganese and zinc abnormalities contribute
to risk Ahmed
and Santosh 2010
- Occupational exposure to mercury increases the risk of hospital
admissions for neurological, Parkinson's or renal diseases Thygesen
et al, 2011
Environmental and dietary
- Early exposure to a rural environment associated with increased
risk (see pesticides)Rajput
et al, 1987
- Working in agriculture, hunting, and forestry has been associated
with increased risk Park
et al, 2005
- Parkinson's disease patients tend to have had
fewer domestic animals at home during their lifetime,
including cows, sheep, pigs, and chickens Kuopio
et al, 1999.
- Dietary vegetables, lutein,
xanthophylls,
xanthins, carbohydrates, monosaccharides, junk food, refined sugar,
lactose, animal fat, total fat, nuts and seeds, tea, Iron, and total
energy associated with increased risk:
Ishihara and Brayne, 2005
- Disease incidence inversely associated with N-3 polyunsaturated
fatty acids and the N-3 precursor alpha-linolenic acid and dietary
fats modified the association of PD risk with pesticide exposure Kamel
et al, 2014.
- Dietary fish, egg, potatoes, bread, alcohol, coffee, tea, niacin,
pantothenic acid, folate
and pyridoxine
associated with reduced risk
Ishihara and Braine,2005 See also Skeie
et al, 2010
- The coffee-PD association was strongest among slow metabolizers
of caffeine who were homozygous carriers of CYP1A2 polymorphisms
Popat
et al, 2011.
- Dietary patterns with a high intake of fruit, vegetables, legumes,
whole grains, nuts, fish, and poultry and a low intake of saturated
fat and a moderate intake of alcohol may protect against Parkinson's
disease.Gao
et al,1997
- Milk intake in midlife has been associoated with a higher risk of
developing Parkinson's disease Park
et al, 2005
- Higher dietary intake of vitamin B6 was associated with a significantly
decreased risk of Parkinson's disease, in smokers De
Lau et al, 2006
- Living near rubber plants and drinking river water asociated with
increased risk in China Wang
et al, 1993
- An inverse association with cigarette smoking has been observedHernan
et al, 2001
- Tobacco
chewing protected and hypertension
increased Parkinson's disease incidence in an Indian study
Das et al, 2010.
- Moderate caffeine
intake may have a protective effect Ascherio
et al, 2001
- Hormone
replacement therapy has little effect but may modify the effects
of caffeine and smoking Simon
et al, 2009
- Black
tea consumption inversely associated with Parkinson's disease
in China Tan
et al, 2008
- Non-aspirin nonsteroidal
anti-inflammatory drugs (NSAIDS) may have a beneficial effect
Ghang
and Power, 2010 Aspirin and salicylate also block the neurotoxic
effects of MPTP Aubin
et al, 1998
- Ibuprofen may reduce the risk of developing Parkinson's disease
Gao
et al, 2011
- Inverse association between the intakes of beta-carotene
or ascorbic
acid and Parkinson's disease Sepcic
et al, 1993
- Flavonoid rich foods (tea, berry fruits, apples, red wine, and orange/orange
juice) have been reported to reduce the risk of developing Parkinson's
disease Gao
et al, 2012
- Parkinson's disease risk is reduced in men working outdoors (possible
relationship with Vitamin D and sunlight) Kenborg
et al, 2010
- Well water drinking as well as exposure to insecticides and pesticides
has been associated with Parkinson's disease Das
et al, 2011
- Hypnotic, anxiolytic or antidepressant drug use for more than 1
year has been associated with Parkinson's disease Dick
et al, 2007
- Under-nutrition is a problem for around 15% of community dwelling
people with Parkinson's disease Jaafar
et al, 2010
- Oral contraceptive use (over 10 years) has been associated with
lower PD risk in women, while short term but not long-term menopausal
hormone therapy was associated with increased risk Liu
et al, 2013
Biochemistry and biomarkers
- Loss of dopamine neurones in the basal ganglia (substantia nigra)
Hornykiewicz
1962
- Glutathione
levels are reduced in the substantia nigra in Parkinson.s disease
Sian
et al, 1994
- Lipid
peroxidation is increased in the substantia nigra Dexter
et al, 1986
- Low plasma levels of octopamine
in early stages D'Andrea
et al, 2010
- Increased plama levels of taurine
in early stages Vitreshchak
et al, 2004
- Vitamin
D deficiency has been associated with Parkinson's disease Evatt
et al, 2008 and vitamin D may be protective Knekt
et al, 2010
- Elevated levels of homocysteine
and methylmalonate in serum and urine Levin
et al, 2010
- Plasma urate
has been associated with a lower risk of Parkinson's disease in men
but not in women O'Reilly
et al, 2010
- High haemoglobin
levels have been associated with Parkinson'sdisease in older men Abbott
et al, 2010
- Mitochondrial complex
V activity is reduced in Parkinson's disease fibroblasts
Del Hoyo et al, 2010
- Increased plasma levels of malondialdehyde
(related to oxidative stress) Sanyal
et al, 2010
- Increased plasma levels of 8-hydroxy-2-deoxyguanosine, a marker
of oxidative DNA damage, with decreased uric acid and increased glutathione
levels Bogdanov
et al, 2008
- Increased plasma levels of DJ-1 Waragai
et al, 2007
- Increased erythrocyte and brain levels of oxidised DJ-1 Akazawa
et al, 2010
- Decreased plasma levels of alpha-synuclein Li
et al, 2007
- Increased serum levels of hepatocyte growth factor Salehi
and Rajaei, 2010
- Lewy body constituents: ACO2 AP2A1 AP2B1 ATIC ATP6V1A CADPS CBR1
CLTC COPA CUL1 DCLK1 DCTN1 DNM1L DPYSL2 DYNC1H1 FBXO2 GAPDH GNAO1
GPI GSN HSPA8 HSP90AB1 MAP2K1 OTUB1 PDIA3 PLEC PRDX5 PRKCB PSMD2 RNF123
S100A9 SNCA SPTAN1 SPTBN1 UBA1 UBA52 UCHL1 VPS35 WDR1 XIA
et al 2008 Leverens
et el, 2007 and many more
, see papers
- Blood biomarkers (gene expression) ALDH1A1 HAP1 HSPA8 PSMC4 SKP1
Molochnikov
et al, 2012
- Low plasma levels of ApoA1 correlated with earlier PD onset Qiang
et al, 2013
- Elevated blood harmane levels in Parkinson's disease Louis
et al, 2014
Microbiome
- Microbiome: Reduced abundance of Prevotellaceae species and greater
abudance of Enterobacteriaceae in faeces of PD patients Scheperjans
et al, 2014
- Reduced Bacteroidetes and Prevotellaceae and increased Enterobacteriaceae
in Parkinson's disease faecal samples: Short chain fatty acids also
decreased Unger
et al, 2016.
Autoantibodies
- Antibodies to melanin have been observed in Parkinson's disease
Double
at al, 2009
- Antibodies to dopamine have been noted Mankovskii
et al, 1993
- Autoantibodies to sympathetic structures Emile
et al, 1980
- Antibodies to TNF and interferon gamma have been noted in Parkinson's
disease Gribova
et al, 2003
- Antibodies to alpha synuclein have been observed in familial Parkinson's
disease Papachroni
et al, 2007 These cross react with antibodies to Herpes simplex
(HSV-1) Caggiu
et al, 2016
- Antibodies to insulin and S100B have been noted in Parkinson's disease
Wilhelm
et al, 2007
- Antibodies to substantia nigra neurones have been noted
Chen et al, 2001
- Anti GM1 ganglioside antibodies have been noted Zappia
et al, 2002
- HSP65 and HSP70 antibodies have been noted in Parkinson's disease
CSF Fiszer
at al, 1996
- Antibodies against the latent membrane protein 1 of the Epstein-Barr
virus label Lewy bodies and cross-react with alpha-synuclein Woulfe
et al, 2000
- Anti-aldolase A autoantibodies Privitera
et al, 2012
- Diagnosis of Parkinson's disease based on disease-specific autoantibody
profiles in human sera. Han
et al, 2012
- ICAM4 PTCD2 FRMD8 CTLA4 MYOT HSH2D FN1 TRIM21 EEF1A1 PABPC3
Comorbidity and others
- Repetitive head trauma (eg boxing dementia
pugilistica ) may increase the risk of developing Parkinson's
diseases
Lolekha et al, 2010
- Parkinson's disease is associated with decreasing darkness of hair
colour Gao
et al, 2009
- Osteoporosis
is common in Parkinson's disease, particularly with insufficient sun
exposure and low calcium intake uric
acid and gout
DeVera
et al, 2008
- Inverse associations of hypertension,
hypercholesterolemia,
and diabetes
mellitus with the risk of Parkinson's disease in Japan Miyake
et al, 2010
- High total baseline cholesterol is associated with increased risk
(Finland) Hu
et al, 2008
- Dietary glycaemic
index negatively correlated with Parkinson's disease Murakami
et al, 2010
- Inverse association with diabetes D'Amelio
et al, 2009
- An inverse association with height Ragonese
et al, 2007
- However, in older patients who has diabetes for more that 10 years
the risk of later developing Parkinson's disease was higher Xu
et al, 2011
- Working in a service occupation negatively associated with PD riskKirke
et al, 2001
- Higher early adult physical exercise is associated with reduced
risk Chen
et al, 2005
- An inverse association between Tumours and Parkinson's disease D'Amelio
et al, 2004
- But an increased incidence of melanoma and skin carcinoma prior
to developing Parkinson's disease Olsen
et al, 2006
- In young women, endometriosis
slightly increases the risk of Parkinson's disease Latourelle
et al, 2010
- Several inflammatory diseases, including rheumatism,
cystitis,
and acute pancreatitis
are associated with an increased risk of developing Parkinson's disease
:
Latourelle et al, 2010 This paper, by examining many estrogen
related disorders, concluded that oestrogen may be a protective factor
in Parkinson's disease See also Gatto
etal, 2014
- Previous general
anaesthesia asoociated with increased riskZorzon
et al, 2002
- Parkinson's disease is less frequent in Afro-Americans Yakoubiam
et al, 2009 and rare in Bulgarian Gypsys Mylanov
et al, 2000
- Parkinson's disease prevalence is slightly higher in those born
in spring as opposed to winter and is also linked to maternal age
Gardener
et al, 2010
- Many patients have sleep disorders: frequent awakening, excessive
daytime sleepiness, nightmares, nocturnal cramps and REM sleep behavior
disorders Hasegawa,
2004 .
- Associated with restless legs syndrome Verbaan
et al, 2010
- Association with Androgenetic alopecia (hairloss and decreased fertility)
Li
et al, 2012
- Anaemia reported as a risk factor, particularly in women Savica
et al, 2012 coupled with slightly lower haemoglobin levels Savica
et al, 2009
- Shorter telomeres have been associated with reduced PD risk Schürks
et al, 2013
- Inverse association between cancer and Parkinson's disease (and
other degenerative disorders) Driver,
2014
Pesticides
and Parkinson’s Disease an open access book chapter
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