Table 2.
Neuroprotective actions of coffee in PD genetic polymorphisms.
| Genetic Polymorphisms |
Reference | Genes/Cells of Interest | Results |
|---|---|---|---|
| Adenosine A2A Receptor (A2AR) | [35] | 1976T/T and 2592Tins/Tins genotypes | Independent coffee-PD association of the A2A 2592C > Tins (rs3032740) polymorphism |
| [36] | Cytochrome P450 1A2 (CYP1A2) | ≠Coffee-PD associations | |
| [37] | Four A2AR (rs5751876, rs71651683, rs3032740 and rs5996696) and three CYP1A2 (rs762551, rs2472304 and rs2470890) | Strong coffee-PD association among CYP1A2 variant allele rs762551 and rs2470890 | |
| Estrogen receptor (ESR) genes | [38] | Estrogen receptor alpha (ESR1), Estrogen receptor beta (ESR2) | ↑ PD risk among female with rs762551 polymorphism of CYP1A2 |
| Nitric Oxide Synthase (NOS) | [39] | NOS2A rs944725 | Significant inverse interaction between caffeine consumption and the NOS2A rs944725 |
| Familial Parkinsonism genetic susceptibility loci | [40] | 10 genome-wide association studies (GWAS) SNPs at or near the alpha-synuclein (SNCA), MAPT, LRRK2, and human leukocyte antigen (HLA) loci | ≠ significant interactions of caffeine intake with several SNPs at or near the SNCA, MAPT, and HLA loci |
| [41] | SNCA, MAPT and LRRK2 | Significant pairwise interaction has been observed between coffee drinking and MAPT H1/H2 haplotype (rs16940806) | |
| Bone marrow stromal cell antigen 1 (BST1) | [42] | BST1 SNPs rs11931532, rs12645693, and rs11724635 | ≠ significant associations between BST1 SNPs rs11931532, rs12645693, and rs11724635 and the risk of sporadic PD |
| Glutamate receptor gene (GRIN2A) | [43] | rs4998386 | Significant interactions from rs4998386 and the neighboring SNPs in GRIN2A |
| [44] | Glutamate receptor gene (GRIN2A) rs4998386 | Heavy caffeine intake & GRIN2A_rs4998386_TC genotype was associated with a ↓ 64% risk reduction Strong significant GRIN2A_rs4998386 genotype ∗ caffeine interaction |
|
| Apolipoprotein E (APOE) | [45] | Genetic polymorphisms of APOE ε2/ε3/ε4, repeat polymorphism (REP1) in the promoter region of the SNCA, MAPT H1/H2 and ubiquitin carboxy-terminal esterase L1 (UCHL1) S18Y | Inverse association between coffee drinking and APOE genotype Most dramatic PD risk in APOE ε2-carriers |
| Adenosine A2A Receptor (A2AR) | [46,47] | CYP1A2 and dopamine transporter (DAT) | Coffee-PD partially associated by CYP1A2, A2AR and DAT |
| Toxicant responsive genes | [48] | 7-ethoxyresorufin O-deethylase (CYP1A1), p-Nitrophenol O-hydroxylase (CYP2E1), glutathione-S-transferase ya (GST-ya), glutathione-S-transferase yc (GST-yc), glutathione S-transferase alpha 4 (GSTA4-4), vesicular monoamine transporter-2 (VMAT-2) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) | MPTP significantly attenuated CYP1A1 and VMAT-2, and augmented CYP2E1, GST-ya, GST-yc and GSTA4-4 expressions and activities |
| Nitric Oxide Synthase (NOS) | [49] | NOS2A rs944725 | ↑ microglial activation and iNOS expression by boosting p38 and ERK1/2 MAP kinase activities |
| Cytochrome oxidase (Cox) expressions | [50] | Cytochrome oxidase 1 (Cox1), cytochrome oxidase 4 (Cox4), cytochrome oxidase 7c (Cox7c) | ↑ Cox1, Cox4 and Cox7c in the striatum of male mice, but not in female mice after receiving a single dose of caffeine ↑ Cox7c mRNA expression in the striatum and in PC-12 cells |
| Heme oxygenase-1 (HO-1) | [51] | Human neuroblastoma SH-SY5Y cells (Pretreatment of SH-SY5Y cells with kahweol) | Pretreatment of SH-SY5Y cells with kahweol significantly reduced 6-OHDA-induced generation of ROS and caspase-3 activation. Protects against 6-OHDA-induced neuronal cell death. Kahweol activated the induction of Nrf2 and HO-1 expression via the phosphatidylinositol 3-kinase (PI3K) and p38 pathway |
| [52,53] | Human neuroblastoma SH-SY5Y cells | ↑ mitochondrial protection in SH-SY5Y cells exposed to H2O2
↓ oxidative stress markers ↓ production of ROS |