Cholecystokinin (CCK) and the CCKA receptor gene polymorphism, and smoking behavior

Takimoto, Takahiro; Terayama, Hayato; Waga, Chikako; Okayama, Takashi; Ikeda, Kazutaka; Fukunishi, Isao; Iwahashi, Kazuhiko

doi:10.1016/j.psychres.2003.06.004

Cited by 10 publications

(6 citation statements)

References 37 publications

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“…6). These data and the results of recent genetic association studies of nicotine dependence and genetic variants of the promoter region of CCK [65] suggest that Cck and Hcrt may affect susceptibility to nicotine sensitization and dependence.…”

Section: The Ubiquitin-proteasome Pathwaymentioning

confidence: 56%

Ventral Tegmental Transcriptome Response to Intermittent Nicotine Treatment and Withdrawal in BALB/cJ, C57BL/6ByJ, and Quasi-Congenic RQI Mice

et al. 2007

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The aim of this study was to identify neurochemical pathways and candidate genes involved in adaptation to nicotine treatment and withdrawal. Locomotor sensitization was assessed in a nicotine challenge test after exposure to intermittent nicotine treatment and withdrawal. About 24 h after the challenge test the ventral tegmentum of the mesencephaion was dissected and processed using oligonucleotide microarrays with 22,690 probe sets (Affymetrix 430A 2.0). Quasi-congenic RQI, and donor BALB/cJ mice developed significant locomotor sensitization, while sensitization was not significant in the background partner, C57BL/6By. Comparing saline treated controls of C57BL/6ByJ and BALB/cJ by a rigorous statistical microarray analysis method we identified 238 differentially expressed transcripts. Quasi-congenic strains B6.Cb4i5-alpha4/Vad and B6.Ib5i7-beta25A/Vad significantly differed from the background strain in 11 and 11 transcripts, respectively. Identification of several cis- and trans-regulated genes indicates that further work with quasi-congenic strains can quickly lead to mapping of Quantitative Trait Loci for nicotine susceptibility because donor chromosome regions have been mapped in quasi-congenic strains. Nicotine treatment significantly altered the abundance of 41, 29, 54, and 14 ventral tegmental transcripts in strains C57BL/6ByJ, BALB/cJ, B6.Cb4i5-alpha4/Vad, and B6.Ib5i7-beta25A/Vad, respectively. Although transcript sets overlapped to some extent, each strain showed a distinct profile of nicotine sensitive genes, indicating genetic effects on nicotine-induced gene expression. Nicotine-responsive genes were related to processes including regulation of signal transduction, intracellular protein transport, proteasomal ubiquitin-dependent protein catabolism, and neuropeptide signaling pathway. Our results suggest that while there are common regulatory mechanisms across inbred strains, even relatively small differences in genetic constitution can significantly affect transcriptome response to nicotine.

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Section: The Ubiquitin-proteasome Pathwaymentioning

confidence: 56%

Ventral Tegmental Transcriptome Response to Intermittent Nicotine Treatment and Withdrawal in BALB/cJ, C57BL/6ByJ, and Quasi-Congenic RQI Mice

et al. 2007

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“…Because of its potential modulation of the dopaminergic system and associated reward pathways, CCK has been investigated in a number of studies as a candidate gene for substance dependence and other behavioral disorders. CCK , along with its two receptors, CCKAR and CCKBR , have been previously associated with anxiety and panic disorders (Maron et al, 2008; Wilson et al, 2012), schizophrenia (Christoforou et al, 2007; Sanjuan et al, 2004), nicotine dependence (Takimoto et al, 2005), and alcohol dependence (Miyasaka et al, 2004; Okubo & Harada, 2001; Okubo et al, 2002). Although one study reported no association between CCK and CCKBR with alcohol dependence (Vanakoski et al, 2001), the study was performed using a Finnish population and did not examine the same significant SNPs that were determined in our study.…”

Section: Discussionmentioning

confidence: 99%

Variants Near CCK Receptors are Associated With Electrophysiological Responses to Pre-pulse Startle Stimuli in a Mexican American Cohort

et al. 2015

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Neurophysiological measurements of the response to prepulse and startle stimuli have been suggested to represent an important endophenotype for both substance dependence and other select psychiatric disorders. We have previously shown, in young adult Mexican Americans (MA), that presentation of a short delay acoustic prepulse, prior to the startle stimuli can elicit a late negative component at about 400 msec (N4S), in the event-related potential (ERP), recorded from frontal cortical areas. In the present study we investigated whether genetic factors associated with this endophenotype could be identified. The study included 420 (age 18 – 30 years) MA men (n=170) and women (n=250). DNA was genotyped using an Affymetrix Axiom Exome1A chip. An association analysis revealed that the CCKAR and CCKBR (cholecystokinin A and B receptor) genes each had a nearby variant that showed suggestive significance with the amplitude of the N4S component to prepulse stimuli. The neurotransmitter cholecystokinin (CCK), along with its receptors, CCKAR and CCKBR, have been previously associated with psychiatric disorders, suggesting that variants near these genes may play a role in the prepulse/startle response in this cohort.

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“…Studies considering mutations in the CCK and CCKAR genes have mainly focused on diseases related to the central and peripheral nervous system, including schizophrenia, panic disorder, Parkinson' s disease, and smoking behavior. [18][19][20][21] Studies on biliary tract-related diseases are rare, with only one study by Srivastava et al 22 that reported an association of the CCKAR Pst I mutation with an increased risk of gallstones (OR = 2.25, 95% CI: 1.2-4.1).…”

Section: Discussionmentioning

confidence: 99%

Variants in CCK and CCKAR genes to susceptibility to biliary tract cancers and stones: A population‐based study in Shanghai, China

Xu¹,

Hsing

Vogtmann

et al. 2013

J of Gastro and Hepatol

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Background and Aim Altered motility of the gallbladder is associated with an increased risk of gallstones and can result in biliary tract cancers. Cholecystokinin (CCK) is an important modulator of gallbladder motility which functions by activating CCK type-A receptor (CCKAR). The aim of this study was to determine whether genetic variants in CCK and CCKAR are associated with the risk of biliary tract cancers and stones. Methods We investigated the associations between 9 single nucleotide polymorphisms (SNPs) in CCK and CCKAR in a population-based case-control study, including 439 biliary tract cancer cases (253 gallbladder, 133 extrahepatic bile duct and 53 ampulla of Vater cancer cases), 429 biliary stone cases, and 447 population controls in Shanghai, China. Results We found that women with the CCKAR rs1800855 AA genotype had an increased risk of gallbladder cancer (odd ratio (OR) =2.37, 95% confidence interval (CI): 1.36–4.14) compared to subjects with the TT genotype, and remained significant after Bonferroni correction (P=0.0056). Additionally, female carriers of the CCKAR haplotype C-T-C-T (rs2071011-rs915889-rs3822222-rs1800855) had a reduced risk of gallbladder cancer (OR=0.61, 95%CI: 0.43–0.86) compared to those with the G-C-C-A haplotype, the association also remained significant after Bonferroni correction. Conclusions These findings suggest that variants in the CCKAR gene may influence the risk of gallbladder cancer in women. Additional studies are needed to confirm our findings.

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Cholecystokinin (CCK) and the CCKA receptor gene polymorphism, and smoking behavior

Cited by 10 publications

References 37 publications

Ventral Tegmental Transcriptome Response to Intermittent Nicotine Treatment and Withdrawal in BALB/cJ, C57BL/6ByJ, and Quasi-Congenic RQI Mice

Ventral Tegmental Transcriptome Response to Intermittent Nicotine Treatment and Withdrawal in BALB/cJ, C57BL/6ByJ, and Quasi-Congenic RQI Mice

Variants Near CCK Receptors are Associated With Electrophysiological Responses to Pre-pulse Startle Stimuli in a Mexican American Cohort

Variants in CCK and CCKAR genes to susceptibility to biliary tract cancers and stones: A population‐based study in Shanghai, China

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