Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023;38(1):31-40.
doi: 10.15605/jafes.037.S8. Epub 2022 Sep 1.

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

Elizabeth Paz-Pacheco  1 , Jose Nevado Jr  2 , Eva Maria Cutiongco-De La Paz  2   3 , Gabriel Jasul Jr  1 , Aimee Yvonne Criselle Aman  2 , Elizabeth Laurize Alejandro-Ribaya  2   3 , Mark David Francisco  1 , Ma Luz Vicenta Guanzon  4 , May Uyking-Naranjo  5 , Cecille Añonuevo-Cruz  1 , Maria Patricia Deanna Maningat  1 , Cristina Jaring  1 , Paulette Nacpil-Dominguez  1 , Aniza Pala-Mohamad  1 , Abigail Uy-Canto  1 , John Paul Quisumbing  1 , Annabelle Marie Lat  1 , Diane Carla Bernardo  1 , Noemie Marie Mansibang  1 , Vincent Sean Ribaya  2   3 , Karell Jo Angelique Calpito  2   3 , Julius Patrick Ferrer  2   3 , Jessica Biwang  2 , Jodelyn Melegrito  2 , Christian Deo Deguit  2 , Carlos Emmanuel Panerio  2
Affiliations

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

Elizabeth Paz-Pacheco et al. J ASEAN Fed Endocr Soc. 2023.

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, 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.

Keywords: Filipino; genetic variants; gliclazide; glimepiride; resistance; sulfonylureas.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Flowchart of participant enrollment and follow-up.
Figure 2
Figure 2
Schematic diagram of data processing and analysis for the gliclazide group. A total of 139 participants (A) and 2,842 SNPs (B) were analyzed to determine the association of genetic variants with poor gliclazide response. Abbreviations: mind – individual missingness; SNP – single nucleotide polymorphism; HWE – Hardy-Weinberg equilibrium; geno – genotypic missingness; MAF – minor allele frequency.
Figure 3
Figure 3
Schematic diagram of data processing and analysis for glimepiride group. A total of 139 participants (A) and 2,842 SNPs (B) were analyzed to determine the association of genetic variants with poor glimepiride response. Abbreviations: mind – individual missingness; SNP – single nucleotide polymorphism; HWE – Hardy-Weinberg equilibrium; geno – genotypic missingness; MAF – minor allele frequency.
See this image and copyright information in PMC

References

    1. Sola D, Rossi L, Schianca GP, et al. . Sulfonylureas and their use in clinical practice. Arch Med Sci. 2015;11(4):840-8. PMID: . PMCID: . 10.5114/aoms.2015.53304. - DOI - PMC - PubMed
    1. Jeon JY, Lee SJ, Lee S, et al. . Failure of monotherapy in clinical practice in patients with type 2 diabetes: The Korean National Diabetes Program. J Diabetes Investig. 2018;9(5):1144-52. PMID: . PMCID: . 10.1111/jdi.12801. - DOI - PMC - PubMed
    1. Jimeno C, Sobrepeña L, Mirasol R. DiabCare 2008: Survey on glycaemic control and the status of diabetes care and complications among patients with type 2 diabetes mellitus in the Philippines. Philipp J Intern Med. 2012;50(1):15-22.
    1. Leiter LA, Shestakova MV, Trubitsyna NP, Piletič M, Satman I. Implementing an optimized glucose-lowering strategy with a novel once daily modified release gliclazide formulation. Diabetes Res Clin Pract. 2016;112:50-6. PMID: . 10.1016/j.diabres.2015.11.001. - DOI - PubMed
    1. Garber A, Henry R, Ratner R, et al. . Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): A randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet. 2009;373(9662):473-81. PMID: . 10.1016/S0140-6736(08)61246-5. - DOI - PubMed

Publication types

MeSH terms

LinkOut - more resources