Table 1.
Gene, SNP | Molecular description | Functional significance | Clinical association |
---|---|---|---|
FAS, −670A > G | A to G substitution within signal transducers and activators of transcription binding sites in the FAS promoter [73] | The −670 A allele is associated with higher level of gene transcription [73] |
Associated with AD risk [74, 75]; other studies failed to show this association [78, 79, 83] Associated with MS risk [72, 80, 81]; Niino et al. [82] failed to show this association |
FAS, −1377G > A | G to A substitution within Sp1 binding site in the FAS promoter [73] | The −1377 G allele is associated with higher level of gene transcription [73] | Associated with AD risk [83] |
TNF-α, −308G > A | G to A substitution in the TNF-α promoter | The −308 A allele has higher transcriptional activity and gene expression than the G allele [113] |
Associated with AD risk; however, data have led to disparate results [105, 109, 110] Increases the risk to develop early onset of sporadic PD [119]. Other studies failed to find this association [118] Associated with ischemic stroke risk, but the results have not been consistent across populations [121–125] |
TNF-α, −850C > T | C to T substitution in the TNF-α promoter | The −850 T allele is associated with a higher level of gene transcription [113] | The TNF −850 T allele synergistically with carriage of the APOE ε4 alleles increase the risk of AD [105, 106]. No positive associations were found in an Italian population [113] |
TNF-α, −1031C > T | C to T substitution in the TNF-α promoter | The −1031 C allele increases TNF expression [105] | Increases the risk of developing an early onset of sporadic PD [120] |
CASP8, −652 6N ins/del | Six-nucleotide insertion/deletion in the CASP8 promoter region | The −652 6N del variant destroys the Sp1-binding site and decreases RNA expression and caspase-8 apoptotic activity [130] | Not studied in neurological disorders |
CASP9, −1263A > G | A to G substitution in the promoter of CASP9 | The −1263 GG genotype enhances the transcriptional activity [141] | Not studied in neurological disorders |
BCL2, −938C > A | C to A substitution in the inhibitory P2 BCL2 promoter | The −938 C allele increases promoter activity and binding of nuclear proteins [147] | Not studied in neurological disorders |
BCL2, rs956572A > G | A to G substitution in the intronic region of BCL2 | The AA genotype is associated with lower Bcl-2 mRNA, protein concentrations and greater cellular sensitivity to stress-induced apoptosis [148] |
Modulates grey matter volume in the ventral striatum of healthy subjects [148] Increases the risk to develop bipolar disorder [149] |
BAX, −248G > A | G to A substitution in the 5′-UTR of BAX | The −248 G variant decreases constitutive Bax expression and increases the Bcl-2/Bax ratio [151, 152] | Not studied in neurological diseases |
TP53, Arg72Pro | Codon 72 of human TP53 has either the sequence CCC, which encodes proline, or CGC, which encodes arginine within a segment that encodes the proline-rich domain, which is important for p53-induced apoptosis [177, 206] | The Arg72 variant has enhanced capacity to trigger apoptosis in neurons [185] and proliferating cells [208–210] and increases neuronal vulnerability to ischemia-induced apoptosis [185] |
The Arg/Arg genotype is associated with poor functional outcome after stroke [185] and traumatic brain injury [212] The Arg/Arg genotype is associated with higher risk for HD [214]; however, a replication study contradicts this association [215] |
MDM2, 309T > G | T to G substitution in the first intron of MDM2, which acts as a transcriptional enhancer region [216] | The 309 T allele increase the affinity of the transcriptional activator Sp1, resulting in higher levels of MDM2 RNA and protein and the subsequent attenuation of the p53 pathway [216, 218] | Not studied in neurological disorders |
SNP single-nucleotide polymorphism