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. 2022 Jun 29;6(8):bvac092.
doi: 10.1210/jendso/bvac092. eCollection 2022 Aug 1.

Variants of SLC2A10 may be Linked to Poor Response to Metformin

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

Variants of SLC2A10 may be Linked to Poor Response to Metformin

Elizabeth Paz-Pacheco et al. J Endocr Soc. .

Abstract

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.

Keywords: SLC2A10; metformin response; pharmacogenetics.

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