BDgene

Core Gene from Gene Prioritization Pathways from PBA (Pathway-based Analysis) Enriched Pathways for Core Genes Enriched Pathways for Cross-disorder Genes

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Study Report

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Basic Info

Reference	Mohammadi, S., 2015 PMID: 25596490
Citation	Mohammadi, S., et al. (2015). "The serotonin transporter (5-HTTLPR) but not serotonin receptor (5-HT2C Cys23Ser) variant is associated with bipolar I disorder in Kurdish population from Western Iran." Neurosci Lett 590: 91-95.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	candidate-gene association study
Sample Size	152 in- and out-patients BID and 173 gender- and age-matched healthy individuals
SNP/Region/Marker Size	2 polymorphisms
Predominant Ethnicity
Population	Kurdish population
Gender	76 females and 76 males for cases, 85 females and 88 males for controls
Age Group	adults : mean age of 35.5 (sd=12.3) years for cases, mean age of 33.7 (sd=11.04) years for controls

Detail Info

Sample Diagnosis	DSMIV-TR
Sample Status	Patients who met the criteria for schizoaffective or schizophrenia or mental retardation and patients with medical condition were excluded from the study. Seven patients with psychotic symptoms more than 2 weeks in the absence of a major mood episode (suspicious to schizoaffective disorder), 2 patients with comorbid mental retardation and 2 patients with medical condition (hepatitis and chronic obstructive pulmonary disorder) were excluded from the study. A positive family history of major mood disorder (at least one first-degree relative suffering from BID, bipolar II disorder or major depressive disorder) existed in 36 patients (24%). Nineteen patients (12.5%) were substance (opiate) dependent. Patients had been treated with lithium, carbamazepin, and valproic acid. A review of medical records and a semi structured interview was used to find the presence of suicide attempt in patients.
Technique	genotyping using PCR
Statistical Method	The allelic frequencies were calculated by the chromosome counting method. The degrees of significance of differences in genotype and allele frequencies of 5-HTTLPR and 5-HT2C between patients and controls were calculated using 2 test. Odds ratios (OR) were calculated as estimates of relative risk for the disease and 95% confidence intervals (CI) were obtained by SPSS logistic regression. Two-tailed Studentâ€™s t-test and ANOVA analysis were also used to compare quantitative data. The categorical variables among groups were compared using 2 test. Statistical significance was assumed at the p < 0.05 level. The Statistical Package for the Social Sciences (SPSS) logistic regression version 16.0 was used for the statistical analysis.
Result Summary	In recessive model (SS vs. LL+LS) the SS genotype was associated with 1.79-fold increased risk of BID (p=0.018). Also, the presence of S allele increased the risk of adult-onset BID by 1.76-fold (p=0.027). No association was detected between 5-HTTLPR genotypes and alleles with suicide attempt. The frequency of 5-HT2C Ser allele in patients and controls were 12.3 and 12.5%, respectively. Mutant allele of HT2C Ser had higher frequency in female (14.7%) than male (10.5%, p=0.27) patients. The frequency of HT2C Ser allele in patients with a family history of BID tended to be higher (15.7%) than those without a family history of the disease (11.8%). The frequency of HT2C Ser allele in suicide attempter women was higher (16.7%) than those without a suicide attempt (14.3%). Our findings demonstrate 5-HTTLPR polymorphism might be a risk factor for BID and adult-onset BID in Kurds population. However, we found the lack of an association between 5-HT2C Cys/Ser variants and the risk of BID.

Other variants reported by this study for BD (count: 2)

Variant Name	Related Gene	Type	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
5HTTLPR	SLC6A4	microsatellite			genotypic P-value=0.037, X²=6.62 in co-dominant model, genotypic P-value=0.98, X²=0 in dominant model, genotypic P-value=0.017, X²=5.65, OR (95%CI, p)=1.79 (1.1-2.88, p=0.018) in recessive model; allelic P-value=0.11, X²=2.5	In recessive model (SS vs. LL + LS) the frequency of SS geno...... In recessive model (SS vs. LL + LS) the frequency of SS genotype was significantly higher in patients (39.5%) than that in controls (26.8%, p = 0.017) that was associated with 1.79-fold increased risk of BID. Also, the presence of S allele increased the risk of adult-onset BID by 1.76-fold. More...	Positive
5-HT2C Cys/Ser	HTR2C	point mutation			genotypic P-value=0.98, X²=0.025, genotypic P-value=0.83, X²=0.36 in females; allelic P-value=0.95, X²=0.004, allelic P-value=0.78, X²=0.073 in females, allelic P-value=0.85, X²=0.05 in males	The frequency of 5-HT2C Ser allele in patients and controls ...... The frequency of 5-HT2C Ser allele in patients and controls were 12.3 and 12.5%, respectively. Mutant allele of HT2C Ser had higher frequency in female (14.7%) than male (10.5%, p=0.27) patients. The frequency of HT2C Ser allele in patients with a family history of BID tended to be higher (15.7%) than those without a family history of the disease (11.8%). The frequency of HT2C Ser allele in suicide attempter women was higher (16.7%) than those without a suicide attempt (14.3%). More...	Negative

Genes reported by this study for BD (count: 2)

Gene	Statistical Values/Author Comments	Result Category
SLC6A4	Our findings demonstrate 5-HTTLPR polymorphism might be a risk factor for BID and adult-onset BID in...... Our findings demonstrate 5-HTTLPR polymorphism might be a risk factor for BID and adult-onset BID in Kurds population. More...	Positive
HTR2C	We found the lack of an association between 5-HT2C Cys/Ser variants and the risk of BID. We found the lack of an association between 5-HT2C Cys/Ser variants and the risk of BID.	Negative