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. 2012 Jun 14;70(1):71–88. doi: 10.1007/s00018-012-1029-y

Table 1.

Clinical association with neurological disorders and functional significance of single-nucleotide polymorphisms in apoptotic genes

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 [121125]

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 [208210] 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