Study Report

Comment on Study

View All Comments on Study

Basic Info

Reference	Frank, B., 2004 PMID: 15389765
Citation	Frank, B., B. Niesler, et al. (2004). "Investigation of the human serotonin receptor gene HTR3B in bipolar affective and schizophrenic patients." Am J Med Genet B Neuropsychiatr Genet 131B(1): 1-5
Disease Type	Bipolar Disorder & Schizophrenia
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	We studied 49 patients with BPAD, 78 patients with SZ as well as 62 control subjects. The extended sample employed screening HTR3B exon 1 consisted of an additional number of 113 bipolar patients and 100 controls.
SNP/Region/Marker Size	11 SNPs
Predominant Ethnicity	Caucasian
Population	German

Detail Info

Sample Diagnosis	DSM-III-R
Technique	Primer sequences, PCR and dHPLC
Statistical Method	Comparison of allele frequencies was applied using twosided X² tests and Fisher's exact test. Significance level was 0.05 not corrected for multiple testing. Furthermore, a correction applying e.g., the Bonferroni formula would be overconservative given the fact that linkage disequilibrium exists between polymorphisms and, therefore, observations for different polymorphisms cannot be regarded as independent. Differences of allele frequencies and 95% confidence intervals (95% CI) were estimated as described using a tool accessible on the internet (http://ihg.gsf.de/cgi-bin/hw/hwa1.pl).
Result Summary	Statistical computation rated most variants as probably non-disease related polymorphisms. However, IVS6 + 31C > T, IVS6 + 40C > A, and 1386T > C were solely detected in bipolar affective patients and in none of the controls. Interestingly, we observed a significant underrepresentation of the 3 bp deletion -100_-102delAAG in an extended sample of 162 bipolar affected patients compared to controls (allele-wise: 8% vs. 15%, P = 0.006, OR = 0.49, 95% CI: 0.3-0.82; genotype-wise: 15,5% vs. 29,0%, P = 0.005, OR = 0.45, 95% CI: 0.26-0.77). We suggest that this deletion may influence translational efficiency, thereby possibly affecting the development of bipolar affective disease.

Genetic factors reported by this study for BD

Other variants reported by this study for BD (count: 6)

Variant Name	Related Gene	Type	Allele Change	Statistical Values	Author Comments	Result Category
HTR3B 386A>C (Tyr129Ser)	HTR3B	point mutation	A>C	Genotypic P-value = 0.04 . OR (95% CI)=0.4 (0.17-0.93); allelic P-value = 0.05, OR (95% CI)=0.48 (0.22-1.02) in the standard sample of bipolar affective patients (n=49) compared with controls (n=62)	Most of the tested SNPs did not reach statistical significan...... Most of the tested SNPs did not reach statistical significance since there was no outstanding difference in allele and genotype distributions between the sample of patients with BPAD or SZ and the control sample More...	Positive
HTR3B 547G>A (Val183Ile)	HTR3B	point mutation	G>A	Genotypic P-value = 0.04. OR (95% CI)=8.5 (0.99-73.27); allelic P-value = 0.05, OR (95% CI)=8.02 (0.95-67.8) in the standard sample of bipolar affective patients (n=49) compared with controls (n=62)	Most of the tested SNPs did not reach statistical significan...... Most of the tested SNPs did not reach statistical significance since there was no outstanding difference in allele and genotype distributions between the sample of patients with BPAD or SZ and the control sample More...	Positive
HTR3B IVS4+12G>A	HTR3B	point mutation	G>A	Genotypic P-value = 0.1. OR (95% CI)=1.22 (0.57-2.61); allelic P-value = 0.14, OR (95% CI)=0.51 (0.87-2.62) in the standard sample of bipolar affective patients (n=49) compared with controls (n=62)	Most of the tested SNPs did not reach statistical significan...... Most of the tested SNPs did not reach statistical significance since there was no outstanding difference in allele and genotype distributions between the sample of patients with BPAD or SZ and the control sample More...	Negative
HTR3B IVS4+11C>T	HTR3B	point mutation	C>T	Genotypic P-value = 0.79. OR (95% CI)=1.32 (0.46-3.8); allelic P-value = 0.62, OR (95% CI)=1.29 (0.47-3.57) in the standard sample of bipolar affective patients (n=49) compared with controls (n=62).	Most of the tested SNPs did not reach statistical significan...... Most of the tested SNPs did not reach statistical significance since there was no outstanding difference in allele and genotype distributions between the sample of patients with BPAD or SZ and the control sample More...	Negative
HTR3B 5'UTR -102delAAG	HTR3B	insertion/deletion		Genotypic P-value = 0.005. OR (95% CI)=0.17 (0.05-0.63); allelic P-value = 0.008, OR (95% CI)=0.2 (0.057-0.7) in the standard sample of bipolar affective patients (n=49) compared with controls (n=62). Genotypic P-value = 0.0076. OR (95% CI)=0.43 (0.23-0.78); allelic P-value = 0.0082, OR (95% CI)=0.47 (0.27-0.83) in the extended sample of bipolar affective patients (n=162) compared with German controls (n=100). Genotypic P-value = 0.005. OR (95% CI)=0.45 (0.26-0.77); allelic P-value = 0.006, OR (95% CI)=0.49 (0.3-0.82) in the extended sample of bipolar affective patients (n=162) compared with German controls (n=162).	The prevalence of the 3 bp deletion in the 5' UTR of HTR3B (...... The prevalence of the 3 bp deletion in the 5' UTR of HTR3B ( -100_ -102delAAG) was much lower in patients with BPAD compared to controls. More...	Positive
HTR3B IVS6+72A>G	HTR3B	point mutation	A>G	Genotypic P-value = 0.42. OR (95% CI)=1.4 (0.63-3.16); allelic P-value = 0.45, OR (95% CI)=1.32 (0.64-2.75) in the standard sample of bipolar affective patients (n=49) compared with controls (n=62)	Most of the tested SNPs did not reach statistical significan...... Most of the tested SNPs did not reach statistical significance since there was no outstanding difference in allele and genotype distributions between the sample of patients with BPAD or SZ and the control sample More...	Negative

Genes reported by this study for BD (count: 1)

Gene	Statistical Values/Author Comments	Result Category
HTR3B	we observed a significant underrepresentation of the 3 bp deletion -100_-102delAAG in an extended sample of 162 bipolar affected patients compared to controls (allele-wise: 8% vs. 15%, P = 0.006, OR = 0.49, 95% CI: 0.3-0.82; genotype-wise: 15, 5% vs. 29, 0%, P = 0.005, OR = 0.45, 95% CI: 0.26-0.77). We suggest that this deletion may influence translational efficiency, thereby possibly affecting the...... We suggest that this deletion may influence translational efficiency, thereby possibly affecting the development of bipolar affective disease. More...	Positive

Genetic factors reported by this study for SZ and/or MDD

Other variants reported by this study for SZ/MDD

Disease	Variant Name	Related Gene	Type	Statistical Values	Description	Result Category
SZ	HTR3B 5'UTR -102delAAG	HTR3B	insertion/deletion	Genotypic P-value = 0.22. OR (95% CI)=0.58 (0.26-1.29); allelic P-value = 0.21, OR (95% CI)=0.62 (0.29-1.31) in the schizophrenia patients (n=78) compared with controls (n=62).	Most of the tested SNPs did not reach statistical significance since there was no outstanding difference in allele and genotype distributions between the sample of patients with BPAD or SZ and the control sample	Negative
SZ	HTR3B IVS6+72A>G	HTR3B	point mutation	Genotypic P-value = 0.46. OR (95% CI)=1.4 (0.68-2.9); allelic P-value = 0.41, OR (95% CI)=1.32 (0.68-2.55) in the schizophrenia patients (n=78) compared with controls (n=62)	Most of the tested SNPs did not reach statistical significance since there was no outstanding difference in allele and genotype distributions between the sample of patients with BPAD or SZ and the control sample	Negative
SZ	HTR3B IVS4+12G>A	HTR3B	point mutation	Genotypic P-value = 0.34. OR (95% CI)=1.54 (0.78-3.07); allelic P-value = 0.16, OR (95% CI)=1.42 (0.87-2.33) in the schizophrenia patients (n=78) compared with controls (n=62).	Most of the tested SNPs did not reach statistical significance since there was no outstanding difference in allele and genotype distributions between the sample of patients with BPAD or SZ and the control sample	Negative
SZ	HTR3B IVS4+11C>T	HTR3B	point mutation	Genotypic P-value = 0.64. OR (95% CI)=1.35 (0.52-3.5); allelic P-value = 0.55, OR (95% CI)=1.32 (0.53-3.29) in the schizophrenia patients (n=78) compared with controls (n=62)	Most of the tested SNPs did not reach statistical significance since there was no outstanding difference in allele and genotype distributions between the sample of patients with BPAD or SZ and the control sample	Negative
SZ	HTR3B 547G>A (Val183Ile)	HTR3B	point mutation	Genotypic P-value = 0.63. OR (95% CI)=2.44 (0.25-24.05); allelic P-value = 0.63, OR (95% CI)=2.41 (0.25-23.48) in the schizophrenia patients (n=78) compared with controls (n=62)	Most of the tested SNPs did not reach statistical significance since there was no outstanding difference in allele and genotype distributions between the sample of patients with BPAD or SZ and the control sample	Negative
SZ	HTR3B 386A>C (Tyr129Ser)	HTR3B	point mutation	Genotypic P-value = 0.87. OR (95% CI)=1.07 (0.55-2.1); allelic P-value = 0.87, OR (95% CI)=1.05 (0.59-1.87) in the schizophrenia patients (n=78) compared with controls (n=62)	Most of the tested SNPs did not reach statistical significance since there was no outstanding difference in allele and genotype distributions between the sample of patients with BPAD or SZ and the control sample	Negative

Genes reported by this study for SZ/MDD

Disease	Gene	Description	Result Category
SZ	HTR3B	Most of the tested SNPs did not reach statistical significance since there was no outstanding difference in allele and genotype distributions between the sample of patients with BPAD or SZ and the control sample	Negative