Study Report
Basic Info
| Reference |
Banerjee E, 200919429092
|
| Citation |
Banerjee E., Sinha S., Chatterjee A. and Nandagopal K. (2009) "No causal role for the G482T and G689T polymorphisms in translation regulation of serotonin transporter (SLC6A4) or association with attention-deficit-hyperactivity disorder (ADHD)." Neurosci Lett, 454(3): 244-8.
|
| Study Design |
family-based |
| Study Type |
Candidate-gene association study |
| Sample Size |
90 ADHD families and 100 controls |
| Predominant Ethnicity |
Indian |
| Population |
India |
| Gender |
80 males and 10 femals |
| Age Group |
Children/Adolescents
:
mean age 7.3 years (SD=2.7)
|
Detail Info
| Summary |
They examined influence of allelic variation on stable secondary structure formation and on seed sequences necessary for microRNA-binding. Furthermore, 90 ADHD cases from India were genotyped for these markers and tested for association with ADHD. The Mfold software was used for secondary structure predictions and miRNA-binding sequences were obtained from the PicTar database. Using a family-based study design they assessed genetic association by means of the haplotype-based haplotype relative risk (HHRR) and transmission disequilibrium test (TDT) statistics. With respect to G689T, previously published TDT data were included in pooled analysis. Secondary structure analysis reveals that G482, U482, G689 and U689 conformers are energetically similar. G482T and G689T polymorphisms do not regulate SLC6A4 translation in cis. From the HHRR, TDT and pooled TDT statistics they infer that these polymorphisms are not associated with risk of ADHD. |
| Total Sample |
100 controls, 165 parents and 90 ADHD cases (75 trios + 15 duos) |
| Sample Collection |
India |
| Diagnosis Description |
ADHD cases were recruited from the Out-Patient Department of MRIH after securing approval from the Institutional Ethics Committee. Diagnosis relied on patients meeting the criteria as per DSM-IV-TR and assessment based on the Conner's rating scale. Patients with pervasive developmental disorder, mental retardation or other neurological problems were excluded. |
| Technique |
Genomic DNA isolation from whole blood lymphocytes was performed as described in (Miller et.al, 1988). The G482T and G689T polymorphisms were amplified using forward (5'-CCGCTTGAATGCTGTGTAACACAC- 3') and reverse primers (5'-GTACCCTTCCAATAATAACCTCC-3') described previously in the DNA Engine Thermal Cycler (MJ Research, PTC-200). For detailed information, please refer to the original publication. |
| Analysis Method |
Allele frequencies and heterozygosity were estimated by TFPGA v.1.3 software. To determine Hardy-Weinberg equilibrium (HWE) proportions they used the Likelihood Ratio test. The non-parametric haplotype-based haplotype relative risk and transmission disequilibrium test (TDT) statistics were computed to assess association and linkage. The un-transmitted parental alleles are considered as ethnically matched controls for transmitted alleles in HHRR. Significance is computed by the standard chi-square statistics. Pooled analysis with published TDT data for G689T included transmissions to a single affected offspring in each family. |
| Result Description |
Secondary structure analysis reveals that G482, U482, G689 and U689 conformers are energetically similar. Unlike G482, the U482 change maps within a loop and this conformer differs in free energy by ~4.4 kcal/mol. While G482T is proximal to various miRNA-binding sequences, it is not part of the seed sequence for any of them. Thus, G482T and G689T polymorphisms do not regulate SLC6A4 translation in cis. From the HHRR, TDT and pooled TDT statistics, both of these polymorphisms are not associated with risk of ADHD. |
SNPs reported by this study (count: 2)
| SNP |
Allele Change |
Risk Allele |
Statistical Values |
Author Comments |
Result of Statistical Analysis |
| rs1042173 |
G482T |
|
HHRR P-value=0.353; TDT P-value=0.25 |
This polymorphism is not associated with risk of ADHD.
This polymorphism is not associated with risk of ADHD.
|
Non-significant
|
| rs3813034 |
G689T |
|
HHRR P-value=0.902; TDT P-value=0.23; pooled TDT P-value=0.47 |
This polymorphism is not associated with risk of ADHD.
This polymorphism is not associated with risk of ADHD.
|
Non-significant
|
Hot Results