Rajanukul Institute

Bangkok, Thailand

Rajanukul Institute

Bangkok, Thailand

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Biernacka J.M.,Mayo Medical School | Sangkuhl K.,Stanford University | Jenkins G.,Mayo Medical School | Whaley R.M.,Stanford University | And 32 more authors.
Translational Psychiatry | Year: 2015

Response to treatment with selective serotonin reuptake inhibitors (SSRIs) varies considerably between patients. The International SSRI Pharmacogenomics Consortium (ISPC) was formed with the primary goal of identifying genetic variation that may contribute to response to SSRI treatment of major depressive disorder. A genome-wide association study of 4-week treatment outcomes, measured using the 17-item Hamilton Rating Scale for Depression (HRSD-17), was performed using data from 865 subjects from seven sites. The primary outcomes were percent change in HRSD-17 score and response, defined as at least 50% reduction in HRSD-17. Data from two prior studies, the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomics Study (PGRN-AMPS) and the Sequenced Treatment Alternatives to Relieve Depression (STAR∗D) study, were used for replication, and a meta-analysis of the three studies was performed (N = 2394). Although many top association signals in the ISPC analysis map to interesting candidate genes, none were significant at the genome-wide level and the associations were not replicated using PGRN-AMPS and STAR∗D data. Top association results in the meta-analysis of response included single-nucleotide polymorphisms (SNPs) in the HPRTP4 (hypoxanthine phosphoribosyltransferase pseudogene 4)/VSTM5 (V-set and transmembrane domain containing 5) region, which approached genome-wide significance (P = 5.03E - 08) and SNPs 5' upstream of the neuregulin-1 gene, NRG1 (P = 1.20E - 06). NRG1 is involved in many aspects of brain development, including neuronal maturation and variations in this gene have been shown to be associated with increased risk for mental disorders, particularly schizophrenia. Replication and functional studies of these findings are warranted.


PubMed | Health Science University, University of Tampere, Rajanukul Institute, University of Würzburg and 12 more.
Type: | Journal: Translational psychiatry | Year: 2015

Response to treatment with selective serotonin reuptake inhibitors (SSRIs) varies considerably between patients. The International SSRI Pharmacogenomics Consortium (ISPC) was formed with the primary goal of identifying genetic variation that may contribute to response to SSRI treatment of major depressive disorder. A genome-wide association study of 4-week treatment outcomes, measured using the 17-item Hamilton Rating Scale for Depression (HRSD-17), was performed using data from 865 subjects from seven sites. The primary outcomes were percent change in HRSD-17 score and response, defined as at least 50% reduction in HRSD-17. Data from two prior studies, the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomics Study (PGRN-AMPS) and the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, were used for replication, and a meta-analysis of the three studies was performed (N=2394). Although many top association signals in the ISPC analysis map to interesting candidate genes, none were significant at the genome-wide level and the associations were not replicated using PGRN-AMPS and STAR*D data. Top association results in the meta-analysis of response included single-nucleotide polymorphisms (SNPs) in the HPRTP4 (hypoxanthine phosphoribosyltransferase pseudogene 4)/VSTM5 (V-set and transmembrane domain containing 5) region, which approached genome-wide significance (P=5.03E-08) and SNPs 5 upstream of the neuregulin-1 gene, NRG1 (P=1.20E-06). NRG1 is involved in many aspects of brain development, including neuronal maturation and variations in this gene have been shown to be associated with increased risk for mental disorders, particularly schizophrenia. Replication and functional studies of these findings are warranted.


Rhucharoenpornpanich O.,Mahidol University | Chamratrithirong A.,Mahidol University | Fongkaew W.,Chiang Mai University | Miller B.A.,Pacific Institute for Research and Evaluation | And 5 more authors.
Journal of Health Communication | Year: 2012

This study describes sexual communication among Thai parents and their teens and identifies variables related to communication about sex in urban Thai families. Data were derived from 420 families whose teenage children ages 13-14 years were randomly selected using the probability proportional to size technique. Interviews were conducted with 1 parent and 1 teenage child in each family. In-depth interviews were also conducted in 30 parents and teens drawn from the same 420 families. Results showed that parents were most likely to talk with their teens about body changes and dating; however, less discussion about sex-related issues, birth control, and HIV/AIDS occurred. More daughters than sons reported frequent discussions with their parents about sex. Parents who believed their teens had been involved in sexual activity were more likely to talk about HIV/AIDS and the difficulty of teenagers having babies, instead of talking about sexual intercourse or when to start having sex. Multiple regression analysis indicated that gender of the child (female), parental religiosity, and parental perception of teen sexual activity were significant predictors of increased sexual communication in Thai families. The findings suggest a need for approaches designed to facilitate communication skills about sex-related issues among Thai parents. © 2012 Taylor and Francis Group, LLC.


Leelawatwattana L.,Prince of Songkla University | Praphanphoj V.,Rajanukul Institute | Prapunpoj P.,Prince of Songkla University
FEBS Journal | Year: 2011

During vertebrate evolution, the N-terminal region of transthyretin (TTR) subunit has undergone a change in both length and hydropathy. This was previously shown to change the binding affinity for thyroid hormones (THs). However, it was not known whether this change affects other functions of TTR. In the present study, the effect of these changes on the binding of TTR to retinol-binding protein (RBP) was determined. Two wild-type TTRs from human and Crocodylus porosus, and three chimeric TTRs, including a human chimeric TTR in which its N-terminal sequence was changed to that of C. porosus TTR (croc/huTTR) and two C. porosus chimeric TTRs (hu/crocTTR in which its N-terminal sequence was changed to that of human TTR and xeno/crocTTR in which its N-terminal sequence was changed to that of Xenopus laevis TTR), were analyzed for their binding to human RBP by native-PAGE followed by immunoblotting and a chemilluminescence assay. The Kd of human TTR was 30.41 ± 2.03 μm, and was similar to that reported for the second binding site, whereas that of crocodile TTR was 2.19 ± 0.24 μm. The binding affinities increased in croc/huTTR (Kd = 23.57 ± 3.54 μm) and xeno/crocTTR (Kd = 0.61 ± 0.16 μm) in which their N-termini were longer and more hydrophobic, but decreased in hu/crocTTR (Kd = 5.03 ± 0.68 μm) in which its N-terminal region was shorter and less hydrophobic. These results suggest an influence of the N-terminal primary structure of TTR on its function as a co-carrier for retinol with RBP. © 2011 The Authors Journal compilation © 2011 FEBS.


Cupp P.K.,University of Kentucky | Atwood K.A.,Pacific Institute for Research and Evaluation | Byrnes H.F.,Pacific Institute for Research and Evaluation | Miller B.A.,Pacific Institute for Research and Evaluation | And 5 more authors.
Journal of Health Communication | Year: 2013

This article reports on a combined family-based substance abuse and HIV-prevention intervention targeting families with 13-14-year-old children in Bangkok, Thailand. Families (n = 340) were randomly and proportionally selected from 7 districts in Bangkok with half randomly assigned to an experimental or control condition. Families in the intervention condition were exposed to 5 interactive booklets about adolescent substance use and risky sexual behavior. Trained health educators followed up by phone to encourage completion of each booklet. Primary outcomes reported in this article include whether the intervention increased the frequency of parent-child communication in general or about sexual risk taking in particular as well as whether the intervention reduced discomfort discussing sexual issues. The authors also tested to see whether booklet completion was associated with communication outcomes at the 6-month follow-up. Multivariate findings indicate that the intervention had a significant impact on the frequency of general parent-child communication on the basis of child reports. The intervention had a marginal impact on the frequency of parent-child communication about sexual issues on the basis of parent reports. Booklet completion was associated with reduced discomfort discussing sex and was marginally associated with frequency of parent-child discussion of sex on the basis of parent reports only. These findings indicate that a family-based program can influence communication patterns. © 2013 Copyright Taylor and Francis Group, LLC.


PubMed | Virginia Commonwealth University, Chiang Mai University, CSN & Associates Co., Mahidol University and 2 more.
Type: Journal Article | Journal: International journal of child and adolescent health | Year: 2014

Data were obtained from face-to-face interviews conducted with 420 randomly selected families (one parent, one 13-14 year old teen) in their homes from seven districts of Bangkok, Thailand. Adolescent risky behaviors that may be influenced by parenting practices and family rituals include alcohol use, cigarette use, and delinquency. Measures include: parental monitoring, parenting style, parental closeness, parental communication, and family rituals. Findings reveal increased alcohol use among Thai adolescents exposed to risks in family rituals. Lower prevalence of cigarette use is indicated among youth exposed to authoritative parenting and greater levels of parental monitoring. Serious delinquency is related to more risks in family rituals, but for girls only. Minor delinquency is related to less rule-setting, but also for girls only. These analyses provide support for using a risk and protective framework for guiding prevention strategies in Thailand. The relationship between family rituals and adolescent behaviors warrants further investigation and especially the elements of family rituals that reflect positive vs. the negative forces in the family dynamics.


Nantharat M.,Chulalongkorn University | Nantharat M.,Rajanukul Institute | Wanitchanon T.,Rajanukul Institute | Amesbutr M.,Rajanukul Institute | And 2 more authors.
Genetics and Molecular Research | Year: 2015

Major depressive disorder (MDD) has been associated with the stress response in the brain, which is controlled by the hypothalamic-pituitary-adrenal (HPA) axis. This HPA negative feedback mechanism acts via the activation of glucocorticoid receptor, which is encoded by the NR3C1 gene. The methylation status at the promoter of NR3C1 has been correlated with traumatic experiences in early life, which develop into mental disorder. The aim of this study was to examine the potential associations between the methylation status of NR3C1 promoter, gene expression, blood plasma cortisol levels, and adulthood MDD. The study was conducted with 29 MDD patients (9 males, 20 females) and 33 normal individuals (7 males, 26 females). Bisulfite pyrosequencing on 7 CpG dinucleotides in the region showed significantly higher methylation levels at the CpG7 in MDD patients. When separated by gender, the methylation levels differed significantly in females, but not in males. No significant differences between NR3C1 gene expression level and plasma cortisol levels of MDD patients and normal controls were observed. These data suggest that higher levels of methylation at the NR3C1 promoter may be associated with MDD in a gender-specific manner. © FUNPEC-RP.


Wangkumhang P.,National Center for Genetic Engineering and Biotechnology BioTeC | Wangkumhang P.,Chulalongkorn University | James Shaw P.,National Center for Genetic Engineering and Biotechnology BioTeC | Chaichoompu K.,National Center for Genetic Engineering and Biotechnology BioTeC | And 9 more authors.
PLoS ONE | Year: 2013

There is considerable ethno-linguistic and genetic variation among human populations in Asia, although tracing the origins of this diversity is complicated by migration events. Thailand is at the center of Mainland Southeast Asia (MSEA), a region within Asia that has not been extensively studied. Genetic substructure may exist in the Thai population, since waves of migration from southern China throughout its recent history may have contributed to substantial gene flow. Autosomal SNP data were collated for 438,503 markers from 992 Thai individuals. Using the available self-reported regional origin, four Thai subpopulations genetically distinct from each other and from other Asian populations were resolved by Neighbor-Joining analysis using a 41,569 marker subset. Using an independent Principal Components-based unsupervised clustering approach, four major MSEA subpopulations were resolved in which regional bias was apparent. A major ancestry component was common to these MSEA subpopulations and distinguishes them from other Asian subpopulations. On the other hand, these MSEA subpopulations were admixed with other ancestries, in particular one shared with Chinese. Subpopulation clustering using only Thai individuals and the complete marker set resolved four subpopulations, which are distributed differently across Thailand. A Sino-Thai subpopulation was concentrated in the Central region of Thailand, although this constituted a minority in an otherwise diverse region. Among the most highly differentiated markers which distinguish the Thai subpopulations, several map to regions known to affect phenotypic traits such as skin pigmentation and susceptibility to common diseases. The subpopulation patterns elucidated have important implications for evolutionary and medical genetics. The subpopulation structure within Thailand may reflect the contributions of different migrants throughout the history of MSEA. The information will also be important for genetic association studies to account for population-structure confounding effects. © 2013 Wangkumhang et al.


Ausavarat S.,Chulalongkorn University | Ausavarat S.,Red Cross | Tongkobpetch S.,Chulalongkorn University | Tongkobpetch S.,Red Cross | And 10 more authors.
BMC Medical Genetics | Year: 2011

Background: The presence of mammary glands distinguishes mammals from other organisms. Despite significant advances in defining the signaling pathways responsible for mammary gland development in mice, our understanding of human mammary gland development remains rudimentary. Here, we identified a woman with bilateral amastia, ectodermal dysplasia and unilateral renal agenesis. She was found to have a chromosomal balanced translocation, 46,XX,t(1;20)(p34.1;q13.13). In addition to characterization of her clinical and cytogenetic features, we successfully identified the interrupted gene and studied its consequences.Methods: Characterization of the breakpoints was performed by molecular cytogenetic techniques. The interrupted gene was further analyzed using quantitative real-time PCR and western blotting. Mutation analysis and high-density SNP array were carried out in order to find a pathogenic mutation. Allele segregations were obtained by haplotype analysis.Results: We enabled to identify its breakpoint on chromosome 1 interrupting the protein tyrosine receptor type F gene (PTPRF). While the patient's mother and sisters also harbored the translocated chromosome, their non-translocated chromosomes 1 were different from that of the patient. Although a definite pathogenic mutation on the paternal allele could not be identified, PTPRF's RNA and protein of the patient were significantly less than those of her unaffected family members.Conclusions: Although ptprf has been shown to involve in murine mammary gland development, no evidence has incorporated PTPRF in human organ development. We, for the first time, demonstrated the possible association of PTPRF with syndromic amastia, making it a prime candidate to investigate for its spatial and temporal roles in human breast development. © 2011 Ausavarat et al; licensee BioMed Central Ltd.


PubMed | Chulalongkorn University and Rajanukul Institute
Type: Journal Article | Journal: Genetics and molecular research : GMR | Year: 2016

Major depressive disorder (MDD) has been associated with the stress response in the brain, which is controlled by the hypothalamic-pituitary-adrenal (HPA) axis. This HPA negative feedback mechanism acts via the activation of glucocorticoid receptor, which is encoded by the NR3C1 gene. The methylation status at the promoter of NR3C1 has been correlated with traumatic experiences in early life, which develop into mental disorder. The aim of this study was to examine the potential associations between the methylation status of NR3C1 promoter, gene expression, blood plasma cortisol levels, and adulthood MDD. The study was conducted with 29 MDD patients (9 males, 20 females) and 33 normal individuals (7 males, 26 females). Bisulfite pyrosequencing on 7 CpG dinucleotides in the region showed significantly higher methylation levels at the CpG7 in MDD patients. When separated by gender, the methylation levels differed significantly in females, but not in males. No significant differences between NR3C1 gene expression level and plasma cortisol levels of MDD patients and normal controls were observed. These data suggest that higher levels of methylation at the NR3C1 promoter may be associated with MDD in a gender-specific manner.

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