The genes encoding the 5HT1Dα and 5HT1Dβ receptors are unchanged in patients with panic disorder

Ohara, Koichi; Xie, Dar-Win; Ishigaki, Tatsuya; Deng, Zonglin; Nakamura, Yuhei; Suzuki, Yasuo; Miyasato, Katsumasa

doi:10.1016/0006-3223(95)00108-5

Cited by 19 publications

(21 citation statements)

References 36 publications

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“…As noted in prior studies, the G129T and G861C SNPs were in absolute linkage disequilibrium with each other [Huang et al, 1999]. The previously reported G-511T, G276A, and T371G SNPs, as well as the dinucleotide deletion at positions À 179/À 178, were not found in this study population [No Èthen et al, 1994;Ohara et al, 1996].…”

Section: Identi®ed In Thesupporting

confidence: 52%

“…In previous scienti®c communications, seven naturally occurring polymorphisms have been reported within the 5-HT 1B receptor gene, including six singlenucleotide polymorphisms (SNPs) and one dinucleotide deletion [No Èthen et al, 1994;Lappalainen et al, 1995;Ohara et al, 1996;Huang et al, 1999]. Several genetic studies have examined potential associations between identi®ed SNPs in the human 5-HT 1B receptor gene and speci®c human phenotypes, including alcoholism, antisocial alcoholism, various responses to antimigraine therapy, suicide, depression, panic disorder, and pathological aggression [Ohara et al, 1996;Lappalainen et al, 1998;MaassenVanDenBrink et al, 1998;Huang et al, 1999]. In one of these studies, Finnish antisocial alcoholics were found to have a higher frequency of one speci®c SNP (a G-to-C substitution at nucleotide position 861) than Finnish control subjects [Lappalainen et al, 1998].…”

Section: Introductionmentioning

confidence: 99%

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Novel and previously reported single‐nucleotide polymorphisms in the human 5‐HT_1B receptor gene: No association with cocaine or alcohol abuse or dependence

et al. 2001

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Evidence from animal self-administration and human genetics studies suggests that the serotonin(1B) (5-HT(1B)) receptor may be involved in modulating responses to cocaine or alcohol. We hypothesize that polymorphisms, including single-nucleotide polymorphisms (SNPs), in the human 5-HT(1B) receptor gene, may be associated with individual differences in vulnerability to cocaine or alcohol abuse or dependence. A total of 210 subjects were studied, including individuals with a primary diagnosis (DSM-IV criteria) of cocaine abuse or dependence, alcohol abuse or dependence, and controls with no history of previous or current illicit drug or alcohol abuse or dependence. Genomic DNA samples were isolated from each individual. For 157 of the subjects, polymerase chain reaction (PCR) was used to amplify the entire coding region of the 5-HT(1B) receptor gene as well as parts of the 5' and 3' untranslated regions. PCR products were sequenced in forward and reverse directions on an automated sequencer. Amplified DNA from an additional 53 subjects was sequenced in the 5' untranslated region to gain additional data on the frequency of one identified SNP. Seven polymorphisms were identified: one novel SNP in the 5' untranslated region (UTR) of the gene (A-161T); one SNP not reported in any published scientific communication (but found to be recorded in GenBank) in the 3' UTR (A1180G); two novel dinucleotide deletions at positions - 184/- 183 and - 182/- 181; and three previously identified SNPs (T-261G, C129T, G861C). Data were stratified by ethnicity and pooled Relative Risk was calculated for combined alcohol abuse and dependence cases and controls, and also for combined cocaine abuse and dependence cases and controls. No significant differences between cases and controls were found.

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Section: Identi®ed In Thesupporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Novel and previously reported single‐nucleotide polymorphisms in the human 5‐HT_1B receptor gene: No association with cocaine or alcohol abuse or dependence

et al. 2001

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“…Our study con®rmed the results of their study and developed the evidence that the G861C of the 5HT1B receptor is not likely to be associated with suicide. Though genetic variations were screened in the coding region of the 5HT1B receptor gene in a Japanese population, no polymorphisms with the change of amino acid sequence were detected [Ohara et al, 1996]. Thus, we concluded that it is as yet unlikely that the 5HT1B receptor is implicated in the susceptibility to suicide in a Japanese population.…”

Section: Resultsmentioning

confidence: 78%

No evidence of an association between 5HT1B receptor gene polymorphism and suicide victims in a Japanese population

et al. 2001

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Serotonergic systems have been reported to mediate the control of aggression and/or impulsivity in humans and to be involved in suicidal behavior. Neurochemical studies showing serotonergic dysfunction in suicide appear to support the functional alteration of serotonergic systems due to gene polymorphisms. Knock-out mice of the 5HT1B receptor gene have been reported to result in increased aggression. We hypothesized that the 5HT1B receptor-mediated serotonergic dysfunction was implicated in suicide through disinhibition of aggression and/or impulsivity. To explore this hypothesis, we examined the association between suicide victims who completed suicide and the 5HT1B receptor gene G861C polymorphism. No significant differences in genotype distribution and allele frequencies were found between suicide victims and controls. Though there is the possibility of failing to detect small effects, these results show no evidence of an association between the 5HT1B receptor gene G861C polymorphism and suicide victims in a Japanese population and indicate that it is unlikely that the 5HT1B receptor is implicated in the susceptibility to suicide.

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“…It is located at 6q14.1, within the region 6q13-q26 that has been implicated as harboring a schizophrenia susceptibility gene (SCZD5). 7 Many mutation scans have identified a number of polymorphisms in the coding sequence and surrounding 5 0 -and 3 0 -untranslated regions (UTRs), [8][9][10][11][12][13][14][15] and over 20 association studies have been published with varied results. 5 The polymorphisms include five missense mutations, including T371G that causes a rare phenylalanineto-cysteine amino-acid change (Phe124Cys) with 124Cys exhibiting higher affinity for various receptor ligands.…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in the 5′-untranslated region of the human serotonin receptor 1B (HTR1B) gene affect gene expression

et al. 2003

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We present evidence of complex balancing regulation of HTR1B transcription by common polymorphisms in its promoter. Computational analysis of the HTR1B gene predicted that a 5 0 segment, spanning common DNA sequence variations, TÀ261G, AÀ161T, and À182INS/ DELÀ181, contained a putative functional promoter. Using a secreted alkaline phosphatase (SEAP) reporter gene system, we found that the haplotype À261G_À182INSÀ181_AÀ161 enhanced transcriptional activity 2.3-fold compared with the haplotype TÀ261_À182INSÀ181_AÀ161. Conversely, À161T reversed this, and the net effect when À261G and À161T were in the same haplotype (À261G_À182INSÀ181_À161T) was equivalent to the major haplotype (TÀ261_À182INSÀ181_AÀ161). Electrophoretic mobility shift experiments showed that À261G and À161T modify the binding of transcription factors (TFs): À261G generates a new AP2 binding site, while alleles AÀ161 and À161T exhibit different binding characteristics to AP1. TÀ261G and AÀ161T were found to be in linkage disequilibrium (LD) with G861C in a European ancestry population. Interestingly, G861C has been reported to be associated with several psychiatric disorders. Our results indicate that HTR1B is the target of substantial transcriptional genetic regulation by common haplotypes, which are in LD with the HTR1B single-nucleotide polymorphism (SNP) most commonly used in association studies. Molecular Psychiatry (2003) 8, 901-910.

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The genes encoding the 5HT1Dα and 5HT1Dβ receptors are unchanged in patients with panic disorder

Cited by 19 publications

References 36 publications

Novel and previously reported single‐nucleotide polymorphisms in the human 5‐HT_1B receptor gene: No association with cocaine or alcohol abuse or dependence

Novel and previously reported single‐nucleotide polymorphisms in the human 5‐HT_1B receptor gene: No association with cocaine or alcohol abuse or dependence

No evidence of an association between 5HT1B receptor gene polymorphism and suicide victims in a Japanese population

Polymorphisms in the 5′-untranslated region of the human serotonin receptor 1B (HTR1B) gene affect gene expression

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The genes encoding the 5HT1Dα and 5HT1Dβ receptors are unchanged in patients with panic disorder

Cited by 19 publications

References 36 publications

Novel and previously reported single‐nucleotide polymorphisms in the human 5‐HT1B receptor gene: No association with cocaine or alcohol abuse or dependence

Novel and previously reported single‐nucleotide polymorphisms in the human 5‐HT1B receptor gene: No association with cocaine or alcohol abuse or dependence

No evidence of an association between 5HT1B receptor gene polymorphism and suicide victims in a Japanese population

Polymorphisms in the 5′-untranslated region of the human serotonin receptor 1B (HTR1B) gene affect gene expression

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Novel and previously reported single‐nucleotide polymorphisms in the human 5‐HT_1B receptor gene: No association with cocaine or alcohol abuse or dependence

Novel and previously reported single‐nucleotide polymorphisms in the human 5‐HT_1B receptor gene: No association with cocaine or alcohol abuse or dependence