Table 2. Result from gene pesticide (GxE) analyses: Parkinson’s Environment and Genes (PEG) and related GxE studies.
Rows refer to either pesticide exposures or genetic factors depending on which one was modelled as having two-levels (see headers).
| N cases / controls | Adj OR (95%CI) | N cases / controls | Adj OR (95%CI) | |
|---|---|---|---|---|
| Dopamine transporter – DAT (5′ A clade & 3′ VNTR 9-repeat) | ||||
|
| ||||
| Kelada et al, 2005[41] | Occupationally Unexposed | Occupationally Exposeda | ||
|
| ||||
| 0 susceptibility alleles | 23/37 | 1.00 | 7/17 | 1.00 |
| 1 | 49/60 | 1.21 (0.62, 2.36) | 14/23 | 1.63 (0.52, 5.15) |
| ≥2 | 59/87 | 1.17 (0.62, 2.23) | 26/15 | 5.66 (1.73, 18.5) |
|
| ||||
| PEG (Ritz et al, 2009[43]) | Occupationally Unexposed (JEM) | Occupationally Exposed (JEM)b | ||
|
| ||||
| 0 susceptibility alleles | 26/26 | 1.00 | 13/18 | 1.00 |
| 1 | 34/46 | 0.70 (0.34, 1.45) | 28/18 | 2.00 (0.71, 5.67) |
| ≥2 | 42/43 | 0.94 (0.46, 1.92) | 36/17 | 2.83 (1.01, 7.92) |
|
| ||||
| PEG (Ritz et al, 2009[43]) | No/Low Ambient Paraquat and Maneb Exposure | High Ambient Paraquat and Maneb Exposurec | ||
|
| ||||
| 0 susceptibility alleles | 65/80 | 1.00 | 4/5 | 0.88 (0.22, 3.48) |
| 1 | 99/117 | 0.98 (0.63, 1.52) | 10/4 | 2.99 (0.88, 10.21) |
| ≥2 | 122/122 | 1.30 (0.85, 2.00) | 24/6 | 4.53 (1.70, 12.09) |
|
| ||||
| Multi-drug resistance protein 1 – ABCB1 (rs1045642 and rs2032582) | ||||
|
| ||||
| Drozdzik et al, 2003d[56] – rs1045642 | CC | CT, TT | ||
|
| ||||
| Unexposed / Exposed PD Cases | 19/7 | – | 29/52 | 4.9 (1.7, 14.6) |
|
| ||||
| Zschiedrich et al, 2009d[58] – rs1045642 | CC | CT, TT | ||
|
| ||||
| Unexposed / Exposed PD Cases | 24/2 | – | 43/17 | 4.74 (1.01-22.31) |
|
| ||||
| Dutheil et al, 2010 [57]- rs1045642 | CC, CT | TT | ||
|
| ||||
| Occupationally OC Unexposed | 27/79 | 1.00 | 8/30 | 0.9 (0.3, 2.5) |
| Occupationally OC Exposed | 27/55 | 1.7 (0.7, 4.3) | 15/16 | 7.2 (2.1, 24.8) |
|
| ||||
| Dutheil et al, 2010 [57]- rs2032582 | GG, GT, GA | TT, TA | ||
|
| ||||
| Occupationally OC Unexposed | 30/88 | 1.00 | 5/21 | 0.90 (0.3, 2.7) |
| Occupationally OC Exposed | 29/60 | 1.90 (0.8, 4.5) | 13/11 | 7.90 (2.2, 28.9) |
|
| ||||
| PEG (Narayan et al, 2015[55]) – Risk Score (rs1045642 & rs2032582) | ≤1 susceptibility allele | ≥2 | ||
|
| ||||
| Low OC exposure | 41/126 | 1.00 | 14/22 | 2.25 (1.01, 5.02) |
| Frequent household OC use without occupational pesticide exposure | 24/59 | 1.62 (0.86, 3.06) | 4/18 | 0.68 (0.21, 2.20) |
| Occupational exposure to other pesticides | 55/90 | 1.89 (1.13, 3.18) | 19/15 | 4.30 (1.89, 9.74) |
| Ambient workplace OC exposure and/or self-reported OC use | 95/151 | 1.96 (1.23, 3.14) | 25/27 | 2.98 (1.48, 6.00) |
|
| ||||
| PEG (Narayan et al, 2015[55]) – Risk Score (rs1045642 & rs2032582) | ≤1 susceptibility allele | ≥2 | ||
|
| ||||
| Low OP exposure | 41/126 | 1.00 | 14/22 | 2.25 (1.01, 5.02) |
| Frequent household OP use without occupational pesticide exposure | 24/59 | 1.62 (0.86, 3.06) | 4/18 | 0.68 (0.21, 2.20) |
| Occupational exposure to other pesticides | 30/56 | 1.69 (0.92, 3.10) | 8/7 | 2.62 (0.87, 7.86) |
| Ambient workplace OP exposure and/or self-reported occupational OP use | 121/185 | 2.05 (1.30, 3.22) | 36/35 | 3.71 (1.96, 7.02) |
|
| ||||
| Paraoxonase – PON1 (L55M and Q192R) | ||||
|
| ||||
| PEG (Lee et al, 2013[65]) – L55M-Q192R | No Ambient Diazinon Exposure | Low/High Ambient Diazinon Exposuree | ||
|
| ||||
| LL-RR | 6/14 | 1.00 | 19/33 | 1.10 (0.35-3.47) |
| LM-QR | 53/100 | 1.16 (0.53-4.05) | 133/175 | 1.47 (0.53-4.05) |
| MM-QQ | 6/14 | 1.16 (0.29-4.62 | 28/23 | 2.43 (0.78-7.56) |
|
| ||||
| PEG (Lee et al, 2013 [65]) – L55M-Q192R | No Ambient Chlorpyrifos Exposure | Low/High Ambient Chlorpyrifos Exposuree | ||
|
| ||||
| LL-RR | 6/14 | 1.00 | 15/28 | 1.19 (0.36-3.92) |
| LM-QR | 53/100 | 1.18 (0.42-3.33) | 115/137 | 1.77 (0.64-4.92 |
| MM-QQ | 6/14 | 1.14 (0.29-4.58) | 26/17 | 3.28 (1.02-10.58) |
|
| ||||
| PEG (Lee et al, 2013[65]) – L55M-Q192R | No Ambient Parathion Exposure | Low/High Ambient Parathion Exposuree | ||
|
| ||||
| LL-RR | 6/14 | 1.00 | 15/29 | 0.99 (0.30-3.25) |
| LM-QR | 53/100 | 1.16 (0.41-3.28) | 117/146 | 1.57 (0.56-4.37) |
| MM-QQ | 6/14 | 1.14 (0.28-4.55) | 22/16 | 2.56 (0.78-8.39) |
|
| ||||
| PEG (Narayan et al, 2013[14]) – Q192R | Occasional Household OP Use | Frequent Household OP Use | ||
|
| ||||
| RR+RQ | 74/133 | 1.00 | 28/48 | 1.03 (0.58, 1.82) |
| 75/120 | 1.09 (0.72, 1.65) | 37/24 | 2.62 (1.42, 4.83) | |
|
| ||||
| Nitric oxide synthase – NOS1 (rs2682826) | ||||
|
| ||||
| Hancock et al, 2008f [73] | Unexposed | Exposed | ||
|
| ||||
| CC | N/A | 1.00 | N/A | 3.52 (1.78, 6.95) |
| CT+TT | N/A | 1.00 | N/A | 1.23 (0.63, 2.40) |
|
| ||||
| PEG (Paul et al, 2015[80]) | Occasional Household OP Use | Frequent Household OP Use | ||
|
| ||||
| CC | 103/124 | 1.00 | 35/41 | 1.28 (0.72-2.30) |
| CT+TT | 81/126 | 0.88 (0.57-1.36) | 47/25 | 2.72 (1.45-5.13) |
|
| ||||
| PEG (Paul et al, 2015[80]) | No/Low Ambient OP Exposure | High Ambient OP Exposureg | ||
|
| ||||
| CC | 132/199 | 1.00 | 46/21 | 2.42 (1.27, 4.61) |
| CT+TT | 130/194 | 0.99 (0.70, 1.40) | 48/19 | 4.83 (2.39, 9.73) |
|
| ||||
| Aldehyde dehydrogenase – ALDH2 (clade 1/2 primarily determined by rs737280) | ||||
|
| ||||
| PEG (Fitzmaurice et al, 2014[21]) | Clade 1/1 | Clade 1/2 or 2/2 | ||
|
| ||||
| Unexposed to all ALDH-inhibiting pesticidesh | 76/124 | 1.00 | 96/160 | 1.00 |
| Exposed to any number of pesticides at residence, unexposed at occupation | 29/38 | 1.17 (0.65, 2.10) | 20/49 | 0.73 (0.41, 1.32) |
| Exposed to any number of pesticides at occupation, unexposed at residence | 24/33 | 1.16 (0.63, 2.16) | 29/46 | 1.14 (0.66, 1.95) |
| Exposed to 1 or 2 pesticides at each residence and occupation | 22/23 | 1.58 (0.80, 3.10) | 17/13 | 2.21 (1.01, 4.82) |
| Exposed to ≥ 3 pesticides at residence and 1 to 2 pesticides at occupation | 5/6 | 1.21 (0.35, 4.23) | 8/7 | 1.74 (0.61, 5.03) |
| Exposed to ≥ 3 pesticides at occupation and 1 to 2 pesticides at residence | 4/7 | 0.92 (0.25, 3.43) | 7/4 | 2.80 (0.78, 10.0) |
| Exposed to ≥ 3 pesticides at each residence and occupation | 9/5 | 2.47 (0.78, 7.82) | 11/3 | 5.30 (1.42, 19.8) |
|
| ||||
| s-phase kinase-associated protein 1 – SKP1 (rs2284312) | ||||
|
| ||||
| PEG (Rhodes et al, 2013[95]) | CC | CT/TT | ||
|
| ||||
| Low/No ambient exposure to UPS inhibiting pesticidesi | 79/148 | 1.00 | 29/52 | 1.01 (0.59,1.73) |
| High exposure at either workplace or residence | 68/103 | 1.25 (0.83,1.90) | 33/37 | 1.65 (0.95,2.85) |
| High exposure at both workplace and residence | 43/50 | 1.62 (0.98,2.66) | 29/7 | 7.57 (3.14,18.3) |
|
| ||||
| Major histocompatibility complex class II region: HLA-DR (rs3129882) | ||||
|
| ||||
| PEG (Kannarkat et al, 2015[99]) | No Ambient Pyrethroid Exposure | Ambient Exposure to at least 1 Pyrethroidj | ||
|
| ||||
| AA | 95/117 | 1.00 | 47/58 | 1.04 (0.65, 1.67) |
| GG | 50/81 | 0.73 (0.47, 1.14) | 30/14 | 2.48 (1.24, 4.97) |
|
| ||||
| PEG (Kannarkat et al, 2015[99]) | No Ambient Pyrethroid Exposure | Ambient Exposure to at least 1 Pyrethroidj | ||
|
| ||||
| AA | 95/117 | 1.00 | 47/58 | 0.83 (0.53, 1.28) |
| AG | 172/161 | 0.91 (0.73, 1.13) | 71/66 | 1.25 (0.88, 1.78) |
| GG | 50/81 | 0.82 (0.53, 1.27) | 30/14 | 1.87 (1.08, 3.35) |
Abbreviations: OR=Odds Ratio; OP=Organophosphates; JEM=Job Exposure Matrix; N/A: Not available
a
Subjects considered exposed if reported occupation for 6+ months involved pesticide exposure
b
JEM occupational pesticide exposure (males only, N=347)
c
Ambient exposure at residential addresses
d
Case-only analysis
e
Ambient exposure at residential and workplace addresses
f
Family based study, self-report pesticide exposure
g
Ambient OP exposure at residential and/or workplace addresses
h
Ambient exposure at residences and occupations to ALDH-inhibiting pesticides (benomyl, maneb, mancozeb, ziram, zineb, triflumizole, captan, dieldrin)
i
Ambient exposure at residences and occupations to UPS inhibiting pesticides (benomyl, cyanazine, dieldrin, endosulfan, ferbam, metam, propargite, rotenone, triflumizole, ziram)
j
Ambient pyrethroid exposure at residential and/or workplace addresses