Study Report
Basic Info
| Reference |
Secolin, R.,2012 PMID: 23280964
|
| Citation |
Secolin, R., et al. (2012). "Refinement of chromosome 3p22.3 region and identification of a susceptibility gene for bipolar affective disorder." Am J Med Genet B Neuropsychiatr Genet.
|
| Disease Type |
Bipolar I Disorder |
| Study Design |
case-control |
| Study Type |
Candidate-gene association study |
| Sample Size |
74 families |
| SNP/Region/Marker Size |
94 SNPs |
| Predominant Ethnicity |
|
| Population |
Brazilian |
Detail Info
| Sample Diagnosis |
DSM-IV |
| Sample Status |
This study was approved by the Research Ethics Committee of our institution, and all patients and family members signed a consent form prior to entering the study. We used clinical information and genomic DNA from our previous BPAD familial study [Secolin et al., 2010]. This sample consists of 411 individuals distributed in 74 nuclear families with 96 patients with bipolar I disorder, classified according to DSM-IV criteria (occurrence of one or more full-blown episodes of mania or mixed state characterized by concurrent symptoms of both mania and depression)[American Psychiatric Association, 1994]. |
| Technique |
Genotyping |
| Statistical Method |
We used the TDTae program for family based association analysis [Gordon et al., 2004]. |
| Result Summary |
In the present study, we further refined the region of interest on ch 3p22.3. We genotyped 94 SNPs within the candidate region in 74 families and performed family-based association analysis using a transmission disequilibrium test. One single SNP (rs166508) was associated with the BPAD phenotype (P = 0.0187). This SNP is located within intron 15 of the integrin alpha 9 (ITGA9) gene. ITGA9 encodes the alpha9 subunit of the alpha9beta1 integrin, a membrane glycoprotein receptor for neurotrophins, such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). Quantification of ITGA9 transcripts in the peripheral blood of patients with BPAD and controls showed an upregulation of ITGA9 (Kruskal-Wallis P = 0.0339) in patients with the disease-associated genotype (rs166508*A/A), compared to those with rs166508*G/G and rs166508*G/A genotypes. Sequencing of the ITGA9 cDNA revealed a sequence variant (r.1689_1839del) in rs166508*A carriers, which leads to loss of the entire exon 16. In silico analysis revealed that the deleted region contains three putative microRNA binding sites, which may be involved in the negative regulation of ITGA9. In conclusion, our results confirm previous evidence pointing to a candidate region for BPAD on ch 3p.22.3. In addition, we suggest a molecular substrate that could explain the increase of ITGA9 mRNA levels in probands with BPAD, proposing a new mechanism that could be involved in the genetic susceptibility to the disease. |
SNPs reported by this study for BD (count: 1)
| SNP |
Related Gene(s) |
Allele Change |
Risk Allele |
Statistical Values |
Author Comments |
Result Category |
| rs166508 |
ITGA9
|
A/G |
A |
TDT:P-value = 0.0187
|
The SNP showed a significant association with BD.
The SNP showed a significant association with BD.
|
Positive
|
Genes reported by this study for BD (count: 1)
| Gene |
Statistical Values/Author Comments |
Result Category |
| ITGA9 |
The association results obtained for SNP rs166508 in the present study confirms previous evidence po......
The association results obtained for SNP rs166508 in the present study confirms previous evidence pointing to a candidate region for BPAD on ch 3p.22.3.
More...
|
Positive
|
