CMB-2016v6n2 - page 10

Computational Molecular Biology 2016, Vol.6, No.2, 1-9
http://cmb.biopublisher.ca
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3.2 Genome wide association studies
The combines studies of GWAS of control, incipient, moderate and severe samples are differently identified the
gene expressions based on p-values. We have identified 12 genes that more significantly associated with
transcriptional regulation of cerebral cortex and is potential targets against AD. Using GWAS studies of these
genes which significantly involved in markers and is used for early stage detection of Alzheimer’s disease. The
PTN gene is polymorphism associates with risk of age onset of AD. The PTN SNPs of rs4420638 within APOC1
was strongly linked with PTN of AD of p-value in the logistic of p<0.05. The other genes such as TBC1D2B,
FAR2, LHCGR, EHD1, KCNA5, GPR22, WDFY3 and ITGBL1 genes also has significant SNPs that logistically
associated with AD (Table 4).
Table 4 GWAS analysis of disease genes predicted based on pharmacogenomic properties
Gene SNP AA Protein ID Orthologous Homologues
Predicted Score Median Prediction Score Median
PTN Rs61735090 A151S NP_002816 Tolerated 0.16 3.16 Damaging 0.03 4.32
TBC1D2B Rs3743070 E459K NP_055894 Damaging 0.05 2.58 Damaging 0.01 2.54
FAR2 Rs61742376 C111W NP_060569 Damaging 0.03 2.03 Damaging 0.00 3.79
Rs61742378 V115G NP_060569 Damaging 0.00 2.03 Damaging 0.00 3.79
Rs79585031 K176N NP_060569 Tolerated 0.20 2.03 Damaging 0.00 3.79
LHCGR Rs78773563 I161K NP_000224 Damaging 0.00 2.53 Damaging 0.00 3.36
Rs4539842 L16Q NP_000224 Damaging 0.04 2.94 Damaging 0.01 4.32
EHD1 Rs117115792 L141V NP_006786 Tolerated 0.81 2.83 Damaging 0.00 4.32
Rs3205255 G65R NP_006786 Damaging 0.00 2.83 Damaging 0.00 4.32
KCNA5 Rs71584818 E33V NP_002225 Damaging 0.00 3.64 Damaging 1.00 4.18
Rs1056463 L138Q NP_002225 Damaging 0.00 2.64 Damaging 0.01 4.01
Rs41276730 L185M NP_002225 Damaging 0.04 2.65 Damaging 0.01 4.01
Rs35853292 E211D NP_002225 Tolerating 0.12 2.66 Damaging 0.04 4.01
Rs77281462 R212C NP_002225 Damaging 0.00 2.66 Damaging 0.00 4.01
Rs3197074 R214G NP_002225 Damaging 0.01 2.65 Damaging 0.01 4.01
WDFY3 Rs75223180 V3203M NP_055806 Tolerated 0.07 2.02 Damaging 0.00 2.72
Rs60562427 S2693F NP_055806 Damaging 0.01 1.99 Damaging 0.00 2.72
Rs111848052 L2196P NP_055806 Damaging 0.01 2.02 Damaging 0.00 2.72
Rs112219413 N2096S NP_055806 Tolerated 0.10 2.01 Damaging 0.02 2.72
Rs3098927 S1830F NP_055806 Damaging 0.02 2.21 Damaging 0.01 2.72
ITGBL1 Rs112482922 G259E NP_004782 Tolerated 0.265 1.88 Damaging 0.01 3.12
Using Pharmacogenomic properties of biomarkers prediction on based on gene-drug interaction. The PTN gene is
interacting with Ozone co-treated with Chlorine results in increased expression of PTN mRNA. The TBC1D2B is
strongly interacting with plant extracts results in increased expression of TBC1D2B mRNA to control AD. The
LHCGR gene is strongly interacting with Melatonin, resveratrol and Sodium Fluoride has increase expression of
mRNA to control the AD but the Particulate Matter are decreases the mRNA expression to regulate mRNA
expression to stop the development of brain cells to control AD. The KCNA5 gene is interacting with Acrolein
results in increased expression of KCNA5 gene that regulate the AD expression in transcriptional levels of
cerebral cortex. Another drug such as Rotenon also interacts with KCNA5 that inhibit the reaction of transcription
expression and stop ion gateway channels. Resveratrol affects the reaction geranylgeranylacetone results in
increased expression of KCNA5 protein. Zinc deficiency results in decreased expression of KCNA5 mRNA. The
WDFY3 gene is strongly interacting with APP protein modified form binds to Aluminum which results in
decreased expression of WDFY3 mRNA. Nanotubes, Carbon co-treated with calfactant results in increased
expression of WDFY3 protein. The overall results shows PTN, TBC1D1B, LHCGR, KCNA5 and WDFY5 are
Pharmacologically interacting with different drugs that potentially targets for AD treatment.