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

Authors

  • Elizabeth Paz-Pacheco University of the Philippines - Philippine General Hospital
  • Jose Nevado Jr. University of the Philippines Manila https://orcid.org/0000-0002-5730-7105
  • Eva Maria Cutiongco-de la Paz University of the Philippines Manila https://orcid.org/0000-0002-8131-4639
  • Gabriel Jasul Jr. University of the Philippines - Philippine General Hospital
  • Aimee Yvonne Criselle Aman University of the Philippines Manila https://orcid.org/0000-0002-6528-1451
  • Elizabeth Laurize Alejandro - Ribaya University of the Philippines Manila https://orcid.org/0000-0002-6494-3767
  • Mark David Francisco University of the Philippines - Philippine General Hospital https://orcid.org/0000-0002-5760-1320
  • Ma. Luz Vicenta Guanzon Corazon Locsin Montelibano Memorial Regional Hospital, Bacolod City, Negros Occidental, Philippines
  • May Uyking - Naranjo Southern Philippines Medical Center, Davao City, Philippines
  • Ma. Cecilia Añonuevo - Cruz University of the Philippines - Philippine General Hospital https://orcid.org/0000-0001-5328-3348
  • Maria Patricia Deanna Maningat University of the Philippines - Philippine General Hospital
  • Cristina Jaring University of the Philippines - Philippine General Hospital https://orcid.org/0000-0002-3125-9184
  • Paulette Nacpil - Dominguez University of the Philippines - Philippine General Hospital
  • Aniza Pala-Mohamad University of the Philippines - Philippine General Hospital https://orcid.org/0000-0002-0323-4270
  • Abigail Uy-Canto University of the Philippines - Philippine General Hospital
  • John Paul Quisumbing University of the Philippines - Philippine General Hospital https://orcid.org/0000-0002-9527-712X
  • Annabelle Marie Lat University of the Philippines - Philippine General Hospital https://orcid.org/0000-0003-1287-0487
  • Diane Carla Bernardo University of the Philippines - Philippine General Hospital
  • Noemie Marie Mansibang University of the Philippines - Philippine General Hospital
  • Vincent Sean Ribaya University of the Philippines Manila; Philippine Genome Center https://orcid.org/0000-0002-6494-3767
  • Karell Jo Angelique Calpito University of the Philippines Manila; Philippine Genome Center https://orcid.org/0000-0002-8710-5555
  • Julius Patrick Ferrer University of the Philippines Manila; Philippine Genome Center https://orcid.org/0000-0003-4178-0747
  • Jessica Biwang University of the Philippines Manila https://orcid.org/0000-0002-9079-3168
  • Jodelyn Melegrito University of the Philippines Manila https://orcid.org/0000-0001-8230-5665
  • Christian Deo Deguit University of the Philippines Manila https://orcid.org/0000-0003-0759-4035
  • Carlos Emmanuel Panerio University of the Philippines Manila; Philippine Genome Center https://orcid.org/0000-0002-9387-6364

Keywords:

genetic variants, sulfonylureas, resistance, Filipino, gliclazide, glimepiride

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.

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Author Biographies

Elizabeth Paz-Pacheco, University of the Philippines - Philippine General Hospital

Division of Endocrinology, Diabetes and Metabolism

*co-first author

Jose Nevado Jr., University of the Philippines Manila

Institute of Human Genetics, National Institutes of Health

*co-first author

Eva Maria Cutiongco-de la Paz, University of the Philippines Manila

Institute of Human Genetics, National Institutes of Health

Philippine Genome Center, University of the Philippines Diliman, Diliman, Quezon City, Philippines

Gabriel Jasul Jr., University of the Philippines - Philippine General Hospital

Division of Endocrinology, Diabetes and Metabolism

Aimee Yvonne Criselle Aman, University of the Philippines Manila

Institute of Human Genetics, National Institutes of Health

Elizabeth Laurize Alejandro - Ribaya, University of the Philippines Manila

Institute of Human Genetics, National Institutes of Health

Philippine Genome Center, University of the Philippines Diliman, Diliman, Quezon City, Philippines

Mark David Francisco, University of the Philippines - Philippine General Hospital

Division of Endocrinology, Diabetes and Metabolism

Ma. Cecilia Añonuevo - Cruz, University of the Philippines - Philippine General Hospital

Division of Endocrinology, Diabetes and Metabolism

Maria Patricia Deanna Maningat, University of the Philippines - Philippine General Hospital

Division of Endocrinology, Diabetes and Metabolism

Cristina Jaring, University of the Philippines - Philippine General Hospital

Division of Endocrinology, Diabetes and Metabolism

Paulette Nacpil - Dominguez, University of the Philippines - Philippine General Hospital

Division of Endocrinology, Diabetes and Metabolism

Aniza Pala-Mohamad, University of the Philippines - Philippine General Hospital

Division of Endocrinology, Diabetes and Metabolism

Abigail Uy-Canto, University of the Philippines - Philippine General Hospital

Division of Endocrinology, Diabetes and Metabolism

John Paul Quisumbing, University of the Philippines - Philippine General Hospital

Division of Endocrinology, Diabetes and Metabolism

Annabelle Marie Lat, University of the Philippines - Philippine General Hospital

Division of Endocrinology, Diabetes and Metabolism

Diane Carla Bernardo, University of the Philippines - Philippine General Hospital

Division of Endocrinology, Diabetes and Metabolism

Noemie Marie Mansibang, University of the Philippines - Philippine General Hospital

Division of Endocrinology, Diabetes and Metabolism

Vincent Sean Ribaya, University of the Philippines Manila; Philippine Genome Center

Institute of Human Genetics, National Institutes of Health

Philippine Genome Center, University of the Philippines Diliman, Diliman, Quezon City, Philippines

Karell Jo Angelique Calpito, University of the Philippines Manila; Philippine Genome Center

Institute of Human Genetics, National Institutes of Health

Philippine Genome Center, University of the Philippines Diliman, Diliman, Quezon City, Philippines

Julius Patrick Ferrer, University of the Philippines Manila; Philippine Genome Center

Institute of Human Genetics, National Institutes of Health

Philippine Genome Center, University of the Philippines Diliman, Diliman, Quezon City, Philippines

Jessica Biwang, University of the Philippines Manila

Institute of Human Genetics, National Institutes of Health

Jodelyn Melegrito, University of the Philippines Manila

Institute of Human Genetics, National Institutes of Health

Christian Deo Deguit, University of the Philippines Manila

Institute of Human Genetics, National Institutes of Health

Carlos Emmanuel Panerio, University of the Philippines Manila; Philippine Genome Center

Institute of Human Genetics, National Institutes of Health

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2022-09-01

How to Cite

Paz-Pacheco, E., Nevado Jr., J. ., Cutiongco-de la Paz, E. M., Jasul Jr., G. ., Aman, A. Y. C., Alejandro - Ribaya, E. L., Francisco, M. D., Guanzon, M. L. V., Uyking - Naranjo, M., Añonuevo - Cruz, M. C., Maningat, M. P. D., Jaring, C., Nacpil - Dominguez, P., Pala-Mohamad, A., Uy-Canto, A., Quisumbing, J. P., Lat, A. M., Bernardo, D. C., Mansibang, N. M., Ribaya, V. S., Calpito, K. J. A., Ferrer, J. P., Biwang, J., Melegrito, J., Deguit, C. D., & Panerio, C. E. (2022). Genetic Variants Associated with Poor Responsiveness to Sulfonylureas in Filipinos with Type 2 Diabetes Mellitus. Journal of the ASEAN Federation of Endocrine Societies. Retrieved from https://www.asean-endocrinejournal.org/index.php/JAFES/article/view/1743

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