Genetic Variants Associated with Poor Responsiveness to Sulfonylureas in Filipinos with Type 2 Diabetes Mellitus.

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, 3 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.

Variants of SLC2A10 may be Linked to Poor Response to Metformin.

Purpose: A study among Filipinos revealed that only 15% of patients with diabetes achieved glycemic control, and poor response to metformin could be one of the possible reasons. Recent studies demonstrate how genetic variations influence response to metformin. Hence, the present study aimed to determine genetic variants associated with poor response to metformin. Methods: Using a candidate variant approach, 195 adult Filipino participants with newly diagnosed type 2 diabetes mellitus (T2DM) were enrolled in a case-control study. Genomic DNA from blood samples were collected. Allelic and genotypic associations of variants with poor response to metformin were determined using exact statistical methods. Results: Several polymorphisms were nominally associated with poor response to metformin (P uncorr < 0.05). The most notable is the association of multiple variants in the SLC2A10 gene-rs2425911, rs3092412, and rs2425904-with common additive genetic mode of inheritance. Other variants that have possible associations with poor drug response include rs340874 (PROX-AS1), rs815815 (CALM2), rs1333049 (CDKN2B-AS1), rs2010963 (VEGFA), rs1535435 and rs9494266 (AHI1), rs11128347 (PDZRN3), rs1805081 (NPC1), and rs13266634 (SLC30A8). Conclusion: In Filipinos, a trend for the association for several variants was noted, with further observation that several mechanisms may be involved. The results may serve as pilot data for further validation of candidate variants for T2DM pharmacotherapy.

Selected sociodemographic and psychosocial variables related to mothers' preference for childbirth setting in a barangay in Rosario, Cavite

OBJECTIVES: This study aimed to describe selected sociodemographic and psychosocial factors that are related to mothers' preference for childbirth setting in a barangay in Rosario, Cavite. METHODS: This study utilized a descriptive cross-sectional design. An interview guide was developed, pretested, and used in interviewing mothers who had given birth from September 1, 2007 to August 31, 2010. Data collected was encoded and analyzed using Epi-info 3.5.1 to compute for the means and proportions of relevant variables. RESULTS: A total of 271 mothers were interviewed, of whom 53.5% gave birth at health facilities. Mothers who were young adults, had at least graduated from high school, and/or had a family income of greater than Php 10,000 tended to prefer facility-based delivery. Those who had adequate knowledge of child delivery and postpartum complications, as well as those with a positive attitude towards facility-based delivery, gave birth in health facilities. Among the family members, the spouses had greater influence on the decisions of mothers regarding their preference. Whereas doctors appeared to have influenced the decisions of mothers who had facility-based deliveries, midwives influenced those who had home-based deliveries. CONCLUSION: The maternal mortality ratio in Rosario, Cavite and the facility-based delivery rate in the sampled barangay remain higher than the targeted rates. This necessitates more efforts to achieve Millennium Development Goal (MDG) No 5. The findings of this study can serve as a guide in developing health promotion and education intervention focusing on specific age group, significant others, and health providers in order to achieve the desired outcomes.