A summary-statistics-based approach to examine the role of serotonin transporter promoter tandem repeat polymorphism in psychiatric phenotypes.

In genetic studies of psychiatric disorders in the pre-genome-wide association study (GWAS) era, one of the most commonly studied loci is the serotonin transporter (SLC6A4) promoter polymorphism, a 43-base-pair insertion/deletion polymorphism in the promoter region (5-HTTLPR). The genetic association signals between 5-HTTLPR and psychiatric phenotypes, however, have been inconsistent across many studies. Since the polymorphism cannot be tested via available SNP arrays, we had previously proposed an efficient machine learning algorithm to predict the genotypes of 5-HTTLPR based on the genotypes of eight nearby SNPs, which requires access to individual-level genotype and phenotype data. To utilize the advantage of publicly available GWAS summary statistics obtained from studies with very large sample sizes, we develop a GWAS summary-statistics-based approach for testing the variable number of tandem repeat (VNTR) associations with various phenotypes. We first cross-verify the accuracy of the summary-statistics-based approach for 61 phenotypes in the UK Biobank. Since we observed a strong similarity between the predicted individual-level 5-HTTLPR genotype-based approach and the summary-statistics-based approach, we applied our method to the available neurobehavioral GWAS summary statistics data obtained from large-scale GWAS. We found no genome-wide significant evidence for association between 5-HTTLPR and any of the neurobehavioral traits. We did observe, however, genome-wide significant evidence for association between this locus and human adult height, BMI, and total cholesterol. Our summary-statistics-based approach provides a systematic way to examine the role of VNTRs and related types of genetic polymorphisms in disease risk and trait susceptibility of phenotypes for which large-scale GWAS summary statistics data are available.

Preparation of Solid Dispersions of Simvastatin and Soluplus Using a Single-Step Organic Solvent-Free Supercritical Fluid Process for the Drug Solubility and Dissolution Rate Enhancement.

The study was designed to investigate the feasibility of supercritical carbon dioxide (scCO2) processing for the preparation of simvastatin (SIM) solid dispersions (SDs) in Soluplus® (SOL) at temperatures below polymer's glass transition. The SIM content in the SDs experimental design was kept at 10, 20 and 30% to study the effect of the drug-polymer ratio on the successful preparation of SDs. The SIM-SOL formulations, physical mixtures (PMs) and SDs were evaluated using X-ray diffraction (XRD), differential scanning calorimetry (DSC), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), and dissolution studies. The scCO2 processing conditions and drug-polymer ratio were found to influence the physicochemical properties of the drug in formulated SDs. SIM is a highly crystalline drug; however, physicochemical characterisation carried out by SEM, DSC, and XRD demonstrated the presence of SIM in amorphous nature within the SDs. The SIM-SOL SDs showed enhanced drug dissolution rates, with 100% being released within 45 min. Moreover, the drug dissolution from SDs was faster and higher in comparison to PMs. In conclusion, this study shows that SIM-SOL dispersions can be successfully prepared using a solvent-free supercritical fluid process to enhance dissolution rate of the drug.

Quantification of Scopoletin from the Roots of Argyreia Speciosa (Linn. F) Sweet Using HPLC Through the Concept of Design of Experiment.

BACKGROUND: The roots of Argyreia speciosa (Linn. F) Sweet (family: Convolvulaceae) are used in Ayurveda to treat male reproductive and nervous system disorders. OBJECTIVE: Isolation of scopoletin from the roots of Argyreia speciosa, and development and validation of an analytical method using HPLC for the quantification of scopoletin from the root powder of Argyreia speciosa. METHOD: Scopoletin was isolated from chloroform fraction prepared from hydrolyzed methanolic extract and identified using spectral studies. A reverse-phase HPLC-based analytical method was developed and optimized using the Design of Experiment (DoE) approach to estimate scopoletin from the roots of Argyreia speciosa. Scopoletin was separated and quantified using HPLC containing the C18 column and a PDA detector. The optimized mobile phase was methanol: water (pH∼3.2) [25: 75, %v/v]. RESULTS: The Box-Behnken design was used to optimize chromatographic parameters and the extraction procedure. The validation studies showed a linear relationship (r2=0.998) in the range of 1-40 µg/mL. The LOD and LOQ were found to be 0.28 µg/mL and 0.84 µg/mL, respectively, and the recovery values were found to be between 91.94 and 97.86%. The developed analytical method was found to be robust as well. The amount of scopoletin was estimated to be 0.024 ± 0.0016%w/w from dried root powder. CONCLUSION: The recorded chromatogram and amount of scopoletin determined would serve as one of the standardization parameters to access the quality of raw material containing Argyreia speciosa. HIGHLIGHTS: Developed analytical method may be adopted as a part of the standardization procedure for Argyreia speciosa in the quality control laboratory.