GeneSet Information

Tier I GS87128 • Table S1: Genes with significant alterations in expression following acute nicotine treatment in VTA. [DRG]

DESCRIPTION:

Acute nicotine - Nicotine vs. Saline DNA microarray Change in gene expression All the animals received a subcutaneous saline injection once daily for 5 days to habituate them to the injection process. On day 6, animals received a subcutaneous injection of saline or nicotine in saline (2 mg / kg). Animals were killed by cervical dislocation 1, 2, 4, or 6 h following saline or nicotine injection. S-score (significance score) algorithm Change in expression at 6 hours. S-scores (significance score) > / = 2 or < / = -2 consistently in two adjacent time-points from the 1-, 2-, 4- and 6-h time-points. For a comparison between two arrays, an S-score of 2 or ?2 corresponds to a P value of 0.046. (NIF Table ID 339 [192])

LABEL:

Mouse Acute Nicotine vs. Saline

SCORE TYPE:

Correlation

DATE ADDED:

2010-11-03

DATE UPDATED:

2024-04-25

SPECIES:

URI:

http://neuinfo.org/

AUTHORS:

Chen X, Che Y, Zhang L, Putman AH, Damaj I, Martin BR, Kendler KS, Miles MF

TITLE:

RhoA, encoding a Rho GTPase, is associated with smoking initiation.

JOURNAL:

Genes, brain, and behavior Nov 2007, Vol 6, pp. 689-97

ABSTRACT:

We used microarray analysis of acute nicotine responses in mouse brain to choose rationale candidates for human association studies on tobacco smoking and nicotine dependence (ND). Microarray studies on the time-course of acute response to nicotine in mouse brain identified 95 genes regulated in ventral tegmental area. Among these, 30 genes were part of a gene network, with functions relevant to neural plasticity. On this basis and their known roles in drug abuse or synaptic plasticity, we chose the genes RhoA and Ywhag as candidates for human association studies. A synteny search identified human orthologs and we investigated their role in tobacco smoking and ND in a human case-control association study. We genotyped five and three single nucleotide polymorphisms from the RhoA and Ywhag genes, respectively. Both single marker and haplotype analyses were negative for the Ywhag gene. For the RhoA gene, rs2878298 showed highly significant genotypic association with both smoking initiation (SI) and ND (P = 0.00005 for SI and P = 0.0007 for ND). In the allelic analyses, rs2878298 was only significant for SI. In the multimarker haplotype analyses, significant association with SI was found for the RhoA gene (empirical global P values ranged from 9 x 10(-5) to 10(-5)). In all multimarker combinations analyzed, with or without inclusion of the single most significant marker rs2878298, identical risk and protective haplotypes were identified. Our results indicated that the RhoA gene is likely involved in initiation of tobacco smoking and ND. Replication and future model system studies will be needed to validate the role of RhoA gene in SI and ND. PUBMED: 17284169
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Brain (D001921)
Animals (D000818)
Forecasting (D005544)
Humans (D006801)
DNA (D004247)
GTP Phosphohydrolases (D020558)
Mice (D051379)
Gene Regulatory Networks (D053263)
Substance-Related Disorders (D019966)
rhoA GTP-Binding Protein (D020742)
Gene Expression Profiling (D020869)
Case-Control Studies (D016022)
Smoking (D012907)
Injections, Subcutaneous (D007279)
Synteny (D026801)
Microarray Analysis (D046228)
Therapeutics (D013812)
Role (D012380)
Neuronal Plasticity (D009473)
Risk (D012306)
Tyrosine 3-Monooxygenase (D014446)
Tobacco (D014026)
Tobacco Use Disorder (D014029)
Ventral Tegmental Area (D017557)
Oligonucleotide Array Sequence Analysis (D020411)
Dislocations (D004204)
Nerve Tissue Proteins (D009419)
Haplotypes (D006239)
Genes, vif (D016341)
Reference Values (D012016)
Algorithms (D000465)
Polymorphism, Single Nucleotide (D020641)
Injections (D007267)
Association (D001244)
Diagnosis-Related Groups (D003953)
Nicotine (D009538)
brain (MA:0000168)
response to nicotine (GO:0035094)
gene expression (GO:0010467)

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Supported by NIH R01 AA18776 jointly funded by NIAAA and NIDA, and JAX Center for Precision Genetics NIH U54 OD 020351