ABSTRACT
Introduction@# Sulfonylureas (SUs) are commonly used drugs for type 2 diabetes mellitus (T2DM) in the Philippines. This study aimed to associate genetic variants with poor response to gliclazide and glimepiride among Filipinos.@*Methodology@#Two independent, dichotomous longitudinal substudies enrolled 139 and 113 participants in the gliclazide and glimepiride substudies, respectively. DNA from blood samples underwent customized genotyping for candidate genes using microarray. Allelic and genotypic features and clinical associations were determined using exact statistical methods.@*Results@#Three months after sulfonylurea monotherapy, 18 (13%) were found to be poorly responsive to gliclazide, while 7 (6%) had poor response to glimepiride. Seven genetic variants were nominally associated (p<0.05) with poor gliclazide response, while three variants were nominally associated with poor glimepiride response. For gliclazide response, carboxypeptidase-associated variants (rs319952 and rs393994 of AGBL4 and rs2229437 of PRCP) had the highest genotypic association; other variants include rs9806699, rs7119, rs6465084 and rs1234315. For glimepiride response, 2 variants were nominally associated: CLCN6-NPPA-MTHFR gene cluster – rs5063 and rs17367504 – and rs2299267 from the PON2 loci.@*Conclusion@#Genetic variants were found to have a nominal association with sulfonylurea response among Filipinos. These findings can guide for future study directions on pharmacotherapeutic applications for sulfonylurea treatment in this population.
Subject(s)
GliclazideABSTRACT
Objective@#Recent advances in epigenetic studies continue to reveal novel mechanisms of gene regulation and control, however little is known on the role of epigenetics in sensorineural hearing loss (SNHL) in humans. We aimed to investigate the methylation patterns of two regions, one in RB1 and another in GJB2 in Filipino patients with SNHL compared to hearing control individuals. @*Methods@#We investigated an RB1 promoter region that was previously identified as differentially methylated in children with SNHL and lead exposure. Additionally, we investigated a sequence in an enhancer-like region within GJB2 that contains four CpGs in close proximity. Bisulfite conversion was performed on salivary DNA samples from 15 children with SNHL and 45 unrelated ethnically-matched individuals. We then performed methylation-specific real-time PCR analysis (qMSP) using TaqMan® probes to determine percentage methylation of the two regions. @*Results@#Using qMSP, both our cases and controls had zero methylation at the targeted GJB2 and RB1 regions. @*Conclusion@#Our study showed no changes in methylation at the selected CpG regions in RB1 and GJB2 in the two comparison groups with or without SNHL. This may be due to a lack of environmental exposures to these target regions. Other epigenetic marks may be present around these regions as well as those of other HL-associated genes.
Subject(s)
Hearing Loss , MethylationABSTRACT
@#<p style="text-align: justify;"><strong>BACKGROUND AND OBJECTIVE:</strong> This paper aims to describe long-term visions for health research in the Philippines. Ambisyon Natin 2040, an overarching vision for a dynamic country by the year 2040, is its main inspiration as this enables innovation and sustainable development.</p><p style="text-align: justify;"><strong>METHODS:</strong> The health research profile conceptual framework developed by Tugwell et al., (2006) was utilized to structure the articulation of these visions. Review of related literature, reports, and documents and in-depth interviews with key players in health research were conducted.</p><p style="text-align: justify;"><strong>RESULTS:</strong> In view of economic and technological developments in the country, it is expected that in 2040, health research priorities shall be more trans-disciplinary and more advanced. Research on health regulation and ethics will continue to be of importance. A more enabling environment for health research is also envisioned, since majority of research funding is expected to come from government, in addition to more research-friendly laws. More innovative platforms will be utilized to disseminate research results. The increasing international exposure and impact of academic work in the Philippines is also envisaged.</p><p style="text-align: justify;"><strong>CONCLUSION AND RECOMMENDATIONS: </strong>Health research in the Philippines has been benefitted by a lot of gains and advances in the past years. Thus, to create an enabling health research system in the Philippines by 2040, focusing on innovations in health research, increased number of funding sources, and crafting of better policies on health research should be pursued. Sustaining these gains and advancing health research in our country entail collective effort from different stakeholders, both public and private.</p>
Subject(s)
PhilippinesABSTRACT
Objectives@#The highly polymorphic nature of the CYP2D6 gene and its central role in the metabolism of commonly used drugs make it an ideal candidate for pharmacogenetic screening. This study aims to determine the prevalence of CYP2D6 polymorphisms among Filipinos and their association to lung cancer. @*Method@#Forty seven single nucleotide polymorphisms (SNPs) of the CYP2D6 gene were genotyped from DNA samples of 115 cases with lung cancer and age- and sex-matched 115 controls. @*Results@#Results show that 18 out of 47 polymorphisms have significant genotypic variability (>1% for at least 2 genotypes). No variant is associated with lung cancer. However, rs1135840, rs16947 and rs28360521, were found to be highly variable among Filipinos. @*Conclusion@#This study demonstrated that CYP2D6 polymorphisms are present among Filipinos, which, although not found to be associated with lung cancer, can be useful biomarkers for future pharmacogenetic studies. The SNP rs16947 is found to be associated with cancer and timolol-induced bradycardia; the SNP rs1135840, on the other hand, is only shown to be linked with cancer. The genetic variant rs28360521 is known to be associated with low-dose aspirin-induced lower gastrointestinal bleeding.