Sequence variation and linkage disequilibrium in the GABA transporter-1 gene (SLC6A1) in five populations: implications for pharmacogenetic research

<p>Abstract</p> <p>Background</p> <p>GABA transporter-1 (GAT-1; genetic locus <it>SLC6A1</it>) is emerging as a novel target for treatment of neuropsychiatric disorders. To understand how population differences might influence strategies for pharmacogenetic studies, we identified patterns of genetic variation and linkage disequilibrium (LD) in <it>SLC6A1 </it>in five populations representing three continental groups.</p> <p>Results</p> <p>We resequenced 12.4 kb of <it>SLC6A1</it>, including the promoters, exons and flanking intronic regions in African-American, Thai, Hmong, Finnish, and European-American subjects (total n = 40). LD in <it>SLC6A1 </it>was examined by genotyping 16 SNPs in larger samples. Sixty-three variants were identified through resequencing. Common population-specific variants were found in African-Americans, including a novel 21-bp promoter region variable number tandem repeat (VNTR), but no such variants were found in any of the other populations studied. Low levels of LD and the absence of major LD blocks were characteristic of all five populations. African-Americans had the highest genetic diversity. European-Americans and Finns did not differ in genetic diversity or LD patterns. Although the Hmong had the highest level of LD, our results suggest that a strategy based on the use of tag SNPs would not translate to a major improvement in genotyping efficiency.</p> <p>Conclusion</p> <p>Owing to the low level of LD and presence of recombination hotspots, <it>SLC6A1 </it>may be an example of a problematic gene for association and haplotype tagging-based genetic studies. The 21-bp promoter region VNTR polymorphism is a putatively functional candidate allele for studies focusing on variation in GAT-1 function in the African-American population.</p

Pectin extraction from Citron peel (Citrus medica Linn.) and its use in food system

Screening experiments using 25-1 fractional factorial design showed that pH, temperature, and extracting time were the main factors affecting the amount and quality of extracted pectin from Citrus medica Linn. Optimum condition of pectin extraction was studied using central composite design (CCD). Mathematical models relating pH, temperature and extracted time to amount of extracted pectin, equivalent weight, methyl content and anhydrogalacturonic acid content were established. Based on the mathematics models, the condition of pH 2, 100ºC and 105 min was found to be the optimum conditions for pectin extraction from Citrus medica Linn. Mathematical and experimental results were verified. The use of extracted pectin as a gelling agent in pineapple jam revealed no significant difference in gel consistency compared to that of commercial pectin grade 150 (p>0.05). However, the commercial pectin had a higher liking score on the spreadability, texture and overall liking. As a stabilizer in chocolate pasteurised milk, 0.2% of the extracted pectin was required to prevent precipitation of chocolate powder with the similar viscosity obtained from 0.06% κ-carageena

Time to relapse and remission of bipolar disorder: findings from a 1-year prospective study in Thailand

Thawatchai Leelahanaj,1 Ronnachai Kongsakon,2 Somrak Choovanichvong,3 Sookjaroen Tangwongchai,4 Suchat Paholpak,5 Thoranin Kongsuk,6 Manit Srisurapanont7 For the Thai Bipolar Registry Study Group 1Department of Psychiatry and Neurology, Phramongkutklao Hospital, Bangkok, Thailand; 2Department of Psychiatry, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 3Srithanya Hospital, Nonthaburi, Thailand; 4Department of Psychiatry, Chulalongkorn University, Bangkok, Thailand; 5Department of Psychiatry, Khon Kaen University, Khon Kaen, Thailand; 6Prasrimahabhodi Psychiatric Hospital, Ubon Ratchathani, Thailand; 7Department of Psychiatry, Chiang Mai University, Chiang Mai, Thailand Background and methods: This study aimed to determine time to relapse and remission of mood episodes in Thai patients with bipolar disorder (BD). The Thai Bipolar Disorder Registry was a multicenter, prospective, naturalistic, observational study conducted in Thailand. Participants were adult inpatients or outpatients with Diagnostic and Statistical Manual of Mental Disorders bipolar disorder. The diagnosis of bipolar disorder, current psychiatric comorbidity, mood relapse, and mood remission were determined by using the Mini International Neuropsychiatric Interview. Relapse and remission were assessed every 2 months. Results: Of 424 BD participants, 404 (95.3%) were BD I, and 258 (60.8%) were female. At entry, 260 (61.3%) had recovered, and 49 (11.6%) were recovering. During 1-year follow-up (381.7 person-years), 92 participants (21.7%) had 119 relapses or 0.31 (95% confidence interval 0.25&ndash;0.35) episodes per person-year. Among 119 relapses, 58 (48.7%), 39 (32.7%), and 21 (17.6%) of them were depressive, hypomanic, and manic episodes, respectively. Using the Kaplan&ndash;Meier method, we found that 25% of the participants relapsed in 361 days. Of the 400 participants who reached remission, 113 (28.2%) had mood relapses. Of 173 mood events accountable for remission analysis, the median time to remission was 67.5 days (72.5 days for depressive episodes versus 58.0 days for manic episodes, log rank P = 0.014). Conclusions: The 1-year relapse rate in Thai patients with BD was 21.7% or 0.31 episodes per person-year. About one-fifth of recovered patients had mood relapses within 371 days. On average, a mood episode would remit in 67.5 days. Keywords: bipolar disorder, course, outcome, relapse, remission, Tha

The INTERPRET-DD study of diabetes and depression: a protocol

Aim People with diabetes are at an increased risk of developing depression and other psychological disorders. However little is known about the prevalence, correlates, or care pathways in countries other than the UK and the US. A new study, the International Prevalence and Treatment of Diabetes and Depression (INTERPRET-DD) Study aims to address this dearth of knowledge and identify optimal pathways to care across the globe. Method INTERPRET-DD is a two-year longitudinal study, taking place in 16 countries’ diabetes out-patients facilities, investigating the recognition and management of depressive disorders in people with type 2 diabetes. Clinical interviews are used to diagnose depression, with clinical and other data obtained from medical records and through patient interviews. Pathways to care and the impact of treatment for previously unrecognised depression on clinical outcomes and emotional well-being are being investigated. Results Initial evidence indicates a range of pathways to care exist, with few of these based on available recommendations for treatment. Pilot data indicates that the instruments we are using to measure both symptoms and clinical diagnosis of depression are acceptable in our study population and easy to use. Conclusions Our study will increase the understanding of the impact of co-morbid diabetes and depression and identify the most appropriate (country specific) pathways via which patients receive their care. It addresses an important public health problem and lead to recommendations for best practice relevant to the different participating centres with regard to the identification and treatment of people with co-morbid diabetes and depression

Illustration of the 21 bp insertion/deletion polymorphism (long and short alleles) and the insertion/deletion GG allele in the gene

<p><b>Copyright information:</b></p><p>Taken from "Sequence variation and linkage disequilibrium in the GABA transporter-1 gene () in five populations: implications for pharmacogenetic research"</p><p>http://www.biomedcentral.com/1471-2156/8/71</p><p>BMC Genetics 2007;8():71-71.</p><p>Published online 17 Oct 2007</p><p>PMCID:PMC2175509.</p><p></p> Picture (A) shows position of -24794 A/G SNP, 21 bp insertion and GG deletion. Picture (B) shows the sequence for the short and long alleles and the -24794 A/G SNP. The A allele of the -24794 always coincided with the long allele in our populations. Sequence for the GG insertion/deletion polymorphism is presented in picture (C)