Differential expression of the “C” and “T” alleles of the 5‐HT2A receptor gene in the temporal cortex of normal individuals and schizophrenics

Polesskaya, Oxana O.; Sokolov, Boris P.

doi:10.1002/jnr.10173

Cited by 253 publications

(166 citation statements)

References 39 publications

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“…The TT genotype is associated with more 5-HT 2A receptors in healthy volunteers but apparently not in the mood disorders group even though there was the same rank order of binding by genotype (TT4TC4CC). This finding is consistent with Polesskaya and Sokolov (2002), who studied the relationship of the C and T alleles to the expression of the HTR 2A gene in post-mortem brain tissue and found the expression level with the T allele was higher compared with the C allele in schizophrenia and a control group. They did not include a sample with mood disorders.…”

Section: -Htr 2a Gene Polymorphism and Receptor Binding Vd Khait Et Alsupporting

confidence: 90%

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Association of Serotonin 5-HT2A Receptor Binding and the T102C Polymorphism in Depressed and Healthy Caucasian Subjects

Khait

Huang

Zalsman

et al. 2004

Neuropsychopharmacol

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Serotonin 5-HT 2A receptor (5-HT 2A ) binding is reported to be altered in individuals with suicidal behavior, mood disorders, and aggressive-impulsive traits. Genetic association with major depression, suicidal behavior, and aggressive-impulsive traits has not been established. This study examines the possible association of the 5-HT 2A gene C102T polymorphism with the receptor binding kinetics, and clinical overt phenotypes. The study population included 63 healthy volunteers and 152 subjects with mood disorders, 56 of whom had a history of suicide attempts. All were Caucasian. Platelet 5-HT 2A binding kinetics (B max and K D ) were assayed and adjusted for seasonal variation. All subjects were genotyped for the T102C polymorphism. Clinical phenotype was determined by structured clinical interview. The TT genotype was associated with higher B max in all subjects (F ¼ 3.53, df ¼ 2,211; p ¼ 0.03), controlling for diagnosis. Bonferroni-adjusted post hoc testing showed higher binding in the TT compared with TC genotype in the control group (F ¼ 7.56, df ¼ 2,60, p ¼ 0.001), but not in the mood-disordered subjects. No difference was found in genotype and allele distribution between the mood-disordered subjects, with and without suicide attempt history, and controls. B max was not related to a diagnosis of mood disorders.The TT genotype appears associated with higher platelet 5-HT 2A B max in the healthy population, but this genotypic effect appears absent in mood disorders and unrelated to psychopathology.

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Section: -Htr 2a Gene Polymorphism and Receptor Binding Vd Khait Et Alsupporting

confidence: 90%

“…Turecki et al (2003) found that higher 5-HT 2A binding in the brain is associated with the T102C polymorphism in the 5-HT 2A gene independently of suicide, although others disagree (Hrdina and Du, 2001). The T and C alleles may show differential expression (Polesskaya and Sokolov 2002;Bray et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Association of Serotonin 5-HT2A Receptor Binding and the T102C Polymorphism in Depressed and Healthy Caucasian Subjects

Khait

Huang

Zalsman

et al. 2004

Neuropsychopharmacol

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“…Therefore, disease risk alleles can be mapped by taking advantage of LD relationships to neighboring alleles of genetic markers, and, this way, multiple silent polymorphisms have been found to be associated with human diseases [30]. For example, a link has been found between the silent SNP 102C/T of the 5-HT2A receptor gene in the temporal cortex and the pathogenesis of schizophrenia [31]. Jones and colleagues have shown that silent polymorphisms of the angiotensin-2 receptor increase cardiovascular risk in hypertension [32], while Arriba-Mendez and colleagues have found that when the C allele is present in the silent SNP 927T/C, male children may be predisposed to asthma and atopic dermatitis [33].…”

Section: Discussionmentioning

confidence: 99%

The two single nucleotide polymorphisms in the H37/RBM5 tumour suppressor gene at 3p21.3 correlated with different subtypes of non-small cell lung cancers

Koegel

Phan

et al. 2007

Lung Cancer

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SummaryAllele loss and genetic alteration in chromosome 3p, particularly in 3p21.3 region, are the most frequent and the earliest genomic abnormalities found in lung cancer. Multiple 3p21.3 genes exhibit various degrees of tumour suppression activity suggesting that 3p21.3 genes may function as an integrated tumour suppressor region through their diverse biological activities. We have previously demonstrated growth inhibitory effects and tumour suppression mechanism of the H37/RBM5 gene which is one of the 19 genes residing in the 370kb minimal overlap region at 3p21.3. In the current study, in an attempt to find, if any, mutations in the H37 coding region in lung cancer cells, we compared nucleotide sequences of the entire H37 gene in tumour vs. adjacent normal tissues from 17 non-small cell lung cancer (NSCLC) patients. No mutations were detected, instead, we found the two silent single nucleotide polymorphisms (SNPs), C1138T and C2185T, within the coding region of the H37 gene. In addition, we found that specific allele types at these SNP positions are correlated with different histological subtypes of NSCLC; tumours containing heterozygous alleles (C+T) at these SNP positions are more likely to be associated with adenocarcinoma (AC) whereas homozygous alleles (either C or T) are associated with squamous cell carcinoma (SCC) (p=0.0098). We postulate that, these two silent polymorphisms may be in linkage disequilibrium (LD) with a disease causative allele in the 3p21.3 tumour suppressor region which is packed with a large number of important genes affecting lung cancer development. In addition, because of prevalent loss of heterozygosity (LOH) detected at 3p21.3 which precedes lung cancer initiation, these SNPs may be developed into a marker screening for the high risk individuals. Keywords lung cancer; H37/RBM5/Luca15; single nucleotide polymorphism; 3p21.3; tumour suppressor gene; linkage disequilibrium; loss of heterozygosity

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“…Conceivably, the distinct association between the 5-HT2A receptor 102T-C polymorphism and pure PD in Estonian and Japanese samples may point to a specific influence of this genetic variant on predisposition to pure PD that may lose its strength in comorbid phenotypes of PD. There is also an observation that the C allele has a lower expression than the T allele, indicating a functional role for the 102T-C polymorphism (Polesskaya and Sokolov, 2002). The association with the lower expressive activity allele of the 5-HT2A gene, as well as the failure of therapeutic effects or even symptomatic exacerbation in the case of 5-HT2A antagonists in patients with PD, point to the possible beneficial effects of 5-HT2A agonism in the treatment of PD.…”

Section: -Ht Receptor Genesmentioning

confidence: 99%

Serotonin Function in Panic Disorder: Important, But Why?

Maron

Shlik

2005

Neuropsychopharmacol

109

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The essential role of serotonin (5-hydroxytryptamine (5-HT)) system in the neurobiology and pharmacotherapy of panic disorder (PD) continues to be a topic of intensive interdisciplinary research. Interest in the involvement of 5-HT in PD has been fuelled by clinical studies demonstrating that medications increasing the synaptic availability of 5-HT, such as selective 5-HT re-uptake inhibitors, are effective in the treatment of PD. Rival theories of 5-HT deficiency vs excess have attempted to explain the impact of 5-HT function in PD. In the past decade, knowledge of the role of 5-HT in the neurobiology of PD has expanded dramatically due to much new research including experimental, treatment, brain-imaging, and genetic studies. The current review attempts to summarize the new data and their implications. The challenge and treatment studies generally confirm the specific inhibitory influence of 5-HT on panicogenesis. The brainimaging studies in PD patients demonstrate functional and clinically relevant alterations in various elements of 5-HT system affecting the neurocircuitry of panic. The findings of genetic association studies suggest that certain 5-HT-related genes may contribute to the susceptibility to PD; however, these data are rather limited and inconsistent. It appears that, even if not the primary etiological factor in PD, the 5-HT function conveys important vulnerability, as well as adaptive factors. A better understanding of these processes may be critical in achieving progress in the treatment of patients suffering from PD.

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Differential expression of the “C” and “T” alleles of the 5‐HT2A receptor gene in the temporal cortex of normal individuals and schizophrenics

Cited by 253 publications

References 39 publications

Association of Serotonin 5-HT2A Receptor Binding and the T102C Polymorphism in Depressed and Healthy Caucasian Subjects

Association of Serotonin 5-HT2A Receptor Binding and the T102C Polymorphism in Depressed and Healthy Caucasian Subjects

The two single nucleotide polymorphisms in the H37/RBM5 tumour suppressor gene at 3p21.3 correlated with different subtypes of non-small cell lung cancers

Serotonin Function in Panic Disorder: Important, But Why?

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