The piccolo intronic single nucleotide polymorphism rs13438494 regulates dopamine and serotonin uptake and shows associations with dependence-like behavior in genomic association study

K. Uno, D. Nishizawa, S. Seo, K. Takayama, S. Matsumura, N. Sakai, K. Ohi, Toshitaka Nabeshima, R. Hashimoto, N. Ozaki, J. Hasegawa, N. Sato, F. Tanioka, H. Sugimura, K. I. Fukuda, S. Higuchi, H. Ujike, T. Inada, Nakao Iwata, I. Sora & 10 others M. Iyo, N. Kondo, M. J. Won, N. Naruse, K. Uehara-Aoyama, M. Itokawa, M. Yamada, K. Ikeda, Y. Miyamoto, A. Nitta

Research output: Contribution to journalArticle

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Abstract

Piccolo (PCLO) inhibits methamphetamine-induced neuropharmacological effects via modulation of dopamine (DA) uptake and regulation of the transport of synaptic vesicles in neuronal cells. Clinical studies have recently suggested that the single nucleotide polymorphism (SNP) rs13438494 in the intron 24 of the PCLO gene is associated with psychiatric disorder, in the meta-analysis of GWAS. Therefore, in this study, we attempted to evaluate the possible role of the PCLO SNP in the mechanisms of uptake of monoamines. To characterize rs13438494 in the PCLO gene, we constructed plasmids carrying either the C or A allele of the SNP and transiently transfected them into SH-SY5Y cells to analyze genetic effects on the splicing of PCLO mRNA. The C and A allele constructs produced different composition of the transcripts, indicating that the intronic SNP does affect the splicing pattern. We also transfected DA and serotonin (5-hydroxytryptamine; 5-HT) transporters into cells and analyzed their uptakes to elucidate the association to psychiatric disorders. In the cells transfected with the C allele, both the DA and 5-HT uptake were enhanced compared to the A allele. We also conducted a clinical study, in order to clarify the genetic associations. PCLO rs13438494 exhibits a relationship with the symptoms of drug dependence or related parameters, such as the age of first exposure to methamphetamine, eating disorders, tobacco dependence and fentanyl requirement. Our findings suggest that rs13438494 is associated with drug abuse and contributes to the pathogenesis of psychiatric disorders via modulation of neurotransmitter turnover.

Original languageEnglish
Pages (from-to)265-274
Number of pages10
JournalCurrent Molecular Medicine
Volume15
Issue number3
DOIs
Publication statusPublished - 01-05-2015

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Polymorphism
Single Nucleotide Polymorphism
Dopamine
Serotonin
Nucleotides
Alleles
Association reactions
Psychiatry
Methamphetamine
Substance-Related Disorders
Genes
Modulation
Transport Vesicles
Tobacco Use Disorder
Tobacco
Synaptic Vesicles
Genome-Wide Association Study
Fentanyl
Pharmaceutical Preparations
Introns

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology

Cite this

Uno, K. ; Nishizawa, D. ; Seo, S. ; Takayama, K. ; Matsumura, S. ; Sakai, N. ; Ohi, K. ; Nabeshima, Toshitaka ; Hashimoto, R. ; Ozaki, N. ; Hasegawa, J. ; Sato, N. ; Tanioka, F. ; Sugimura, H. ; Fukuda, K. I. ; Higuchi, S. ; Ujike, H. ; Inada, T. ; Iwata, Nakao ; Sora, I. ; Iyo, M. ; Kondo, N. ; Won, M. J. ; Naruse, N. ; Uehara-Aoyama, K. ; Itokawa, M. ; Yamada, M. ; Ikeda, K. ; Miyamoto, Y. ; Nitta, A. / The piccolo intronic single nucleotide polymorphism rs13438494 regulates dopamine and serotonin uptake and shows associations with dependence-like behavior in genomic association study. In: Current Molecular Medicine. 2015 ; Vol. 15, No. 3. pp. 265-274.
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abstract = "Piccolo (PCLO) inhibits methamphetamine-induced neuropharmacological effects via modulation of dopamine (DA) uptake and regulation of the transport of synaptic vesicles in neuronal cells. Clinical studies have recently suggested that the single nucleotide polymorphism (SNP) rs13438494 in the intron 24 of the PCLO gene is associated with psychiatric disorder, in the meta-analysis of GWAS. Therefore, in this study, we attempted to evaluate the possible role of the PCLO SNP in the mechanisms of uptake of monoamines. To characterize rs13438494 in the PCLO gene, we constructed plasmids carrying either the C or A allele of the SNP and transiently transfected them into SH-SY5Y cells to analyze genetic effects on the splicing of PCLO mRNA. The C and A allele constructs produced different composition of the transcripts, indicating that the intronic SNP does affect the splicing pattern. We also transfected DA and serotonin (5-hydroxytryptamine; 5-HT) transporters into cells and analyzed their uptakes to elucidate the association to psychiatric disorders. In the cells transfected with the C allele, both the DA and 5-HT uptake were enhanced compared to the A allele. We also conducted a clinical study, in order to clarify the genetic associations. PCLO rs13438494 exhibits a relationship with the symptoms of drug dependence or related parameters, such as the age of first exposure to methamphetamine, eating disorders, tobacco dependence and fentanyl requirement. Our findings suggest that rs13438494 is associated with drug abuse and contributes to the pathogenesis of psychiatric disorders via modulation of neurotransmitter turnover.",
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Uno, K, Nishizawa, D, Seo, S, Takayama, K, Matsumura, S, Sakai, N, Ohi, K, Nabeshima, T, Hashimoto, R, Ozaki, N, Hasegawa, J, Sato, N, Tanioka, F, Sugimura, H, Fukuda, KI, Higuchi, S, Ujike, H, Inada, T, Iwata, N, Sora, I, Iyo, M, Kondo, N, Won, MJ, Naruse, N, Uehara-Aoyama, K, Itokawa, M, Yamada, M, Ikeda, K, Miyamoto, Y & Nitta, A 2015, 'The piccolo intronic single nucleotide polymorphism rs13438494 regulates dopamine and serotonin uptake and shows associations with dependence-like behavior in genomic association study', Current Molecular Medicine, vol. 15, no. 3, pp. 265-274. https://doi.org/10.2174/1566524015666150330145722

The piccolo intronic single nucleotide polymorphism rs13438494 regulates dopamine and serotonin uptake and shows associations with dependence-like behavior in genomic association study. / Uno, K.; Nishizawa, D.; Seo, S.; Takayama, K.; Matsumura, S.; Sakai, N.; Ohi, K.; Nabeshima, Toshitaka; Hashimoto, R.; Ozaki, N.; Hasegawa, J.; Sato, N.; Tanioka, F.; Sugimura, H.; Fukuda, K. I.; Higuchi, S.; Ujike, H.; Inada, T.; Iwata, Nakao; Sora, I.; Iyo, M.; Kondo, N.; Won, M. J.; Naruse, N.; Uehara-Aoyama, K.; Itokawa, M.; Yamada, M.; Ikeda, K.; Miyamoto, Y.; Nitta, A.

In: Current Molecular Medicine, Vol. 15, No. 3, 01.05.2015, p. 265-274.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The piccolo intronic single nucleotide polymorphism rs13438494 regulates dopamine and serotonin uptake and shows associations with dependence-like behavior in genomic association study

AU - Uno, K.

AU - Nishizawa, D.

AU - Seo, S.

AU - Takayama, K.

AU - Matsumura, S.

AU - Sakai, N.

AU - Ohi, K.

AU - Nabeshima, Toshitaka

AU - Hashimoto, R.

AU - Ozaki, N.

AU - Hasegawa, J.

AU - Sato, N.

AU - Tanioka, F.

AU - Sugimura, H.

AU - Fukuda, K. I.

AU - Higuchi, S.

AU - Ujike, H.

AU - Inada, T.

AU - Iwata, Nakao

AU - Sora, I.

AU - Iyo, M.

AU - Kondo, N.

AU - Won, M. J.

AU - Naruse, N.

AU - Uehara-Aoyama, K.

AU - Itokawa, M.

AU - Yamada, M.

AU - Ikeda, K.

AU - Miyamoto, Y.

AU - Nitta, A.

PY - 2015/5/1

Y1 - 2015/5/1

N2 - Piccolo (PCLO) inhibits methamphetamine-induced neuropharmacological effects via modulation of dopamine (DA) uptake and regulation of the transport of synaptic vesicles in neuronal cells. Clinical studies have recently suggested that the single nucleotide polymorphism (SNP) rs13438494 in the intron 24 of the PCLO gene is associated with psychiatric disorder, in the meta-analysis of GWAS. Therefore, in this study, we attempted to evaluate the possible role of the PCLO SNP in the mechanisms of uptake of monoamines. To characterize rs13438494 in the PCLO gene, we constructed plasmids carrying either the C or A allele of the SNP and transiently transfected them into SH-SY5Y cells to analyze genetic effects on the splicing of PCLO mRNA. The C and A allele constructs produced different composition of the transcripts, indicating that the intronic SNP does affect the splicing pattern. We also transfected DA and serotonin (5-hydroxytryptamine; 5-HT) transporters into cells and analyzed their uptakes to elucidate the association to psychiatric disorders. In the cells transfected with the C allele, both the DA and 5-HT uptake were enhanced compared to the A allele. We also conducted a clinical study, in order to clarify the genetic associations. PCLO rs13438494 exhibits a relationship with the symptoms of drug dependence or related parameters, such as the age of first exposure to methamphetamine, eating disorders, tobacco dependence and fentanyl requirement. Our findings suggest that rs13438494 is associated with drug abuse and contributes to the pathogenesis of psychiatric disorders via modulation of neurotransmitter turnover.

AB - Piccolo (PCLO) inhibits methamphetamine-induced neuropharmacological effects via modulation of dopamine (DA) uptake and regulation of the transport of synaptic vesicles in neuronal cells. Clinical studies have recently suggested that the single nucleotide polymorphism (SNP) rs13438494 in the intron 24 of the PCLO gene is associated with psychiatric disorder, in the meta-analysis of GWAS. Therefore, in this study, we attempted to evaluate the possible role of the PCLO SNP in the mechanisms of uptake of monoamines. To characterize rs13438494 in the PCLO gene, we constructed plasmids carrying either the C or A allele of the SNP and transiently transfected them into SH-SY5Y cells to analyze genetic effects on the splicing of PCLO mRNA. The C and A allele constructs produced different composition of the transcripts, indicating that the intronic SNP does affect the splicing pattern. We also transfected DA and serotonin (5-hydroxytryptamine; 5-HT) transporters into cells and analyzed their uptakes to elucidate the association to psychiatric disorders. In the cells transfected with the C allele, both the DA and 5-HT uptake were enhanced compared to the A allele. We also conducted a clinical study, in order to clarify the genetic associations. PCLO rs13438494 exhibits a relationship with the symptoms of drug dependence or related parameters, such as the age of first exposure to methamphetamine, eating disorders, tobacco dependence and fentanyl requirement. Our findings suggest that rs13438494 is associated with drug abuse and contributes to the pathogenesis of psychiatric disorders via modulation of neurotransmitter turnover.

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