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

Autor: Paz-Pacheco E; Division of Endocrinology, Diabetes and Metabolism, Philippine General Hospital, University of the Philippines Manila, Philippines., Nevado JB Jr; Institutes of Human Genetics, National Institutes of Health, University of the Philippines Manila, Philippines., Cutiongco-de la Paz EMC; Institutes of Human Genetics, National Institutes of Health, University of the Philippines Manila, Philippines., Jasul GV Jr; Division of Endocrinology, Diabetes and Metabolism, Philippine General Hospital, University of the Philippines Manila, Philippines., Aman AYCL; Institutes of Human Genetics, National Institutes of Health, University of the Philippines Manila, Philippines., Ribaya ELA; Institutes of Human Genetics, National Institutes of Health, University of the Philippines Manila, Philippines., Francisco MDG; Division of Endocrinology, Diabetes and Metabolism, Philippine General Hospital, University of the Philippines Manila, Philippines., Guanzon MLVV; Corazon Locsin Montelibano Memorial Regional Hospital, Bacolod City, Negros Occidental, Philippines., Uyking-Naranjo ML; Southern Philippines Medical Center, Davao City, Davao del Sur, Philippines., Añonuevo-Cruz MCS; Division of Endocrinology, Diabetes and Metabolism, Philippine General Hospital, University of the Philippines Manila, Philippines., Maningat MPDD; Division of Endocrinology, Diabetes and Metabolism, Philippine General Hospital, University of the Philippines Manila, Philippines., Jaring CV; Division of Endocrinology, Diabetes and Metabolism, Philippine General Hospital, University of the Philippines Manila, Philippines., Nacpil-Dominguez PD; Division of Endocrinology, Diabetes and Metabolism, Philippine General Hospital, University of the Philippines Manila, Philippines., Pala-Mohamad AB; Division of Endocrinology, Diabetes and Metabolism, Philippine General Hospital, University of the Philippines Manila, Philippines., Canto AU; Division of Endocrinology, Diabetes and Metabolism, Philippine General Hospital, University of the Philippines Manila, Philippines., Quisumbing JPM; Division of Endocrinology, Diabetes and Metabolism, Philippine General Hospital, University of the Philippines Manila, Philippines., Lat AMM; Division of Endocrinology, Diabetes and Metabolism, Philippine General Hospital, University of the Philippines Manila, Philippines., Bernardo DCC; Division of Endocrinology, Diabetes and Metabolism, Philippine General Hospital, University of the Philippines Manila, Philippines., Mansibang NMM; Division of Endocrinology, Diabetes and Metabolism, Philippine General Hospital, University of the Philippines Manila, Philippines., Calpito KJAC; Institutes of Human Genetics, National Institutes of Health, University of the Philippines Manila, Philippines., Ribaya VSD; Institutes of Human Genetics, National Institutes of Health, University of the Philippines Manila, Philippines., Ferrer JPY; Institutes of Human Genetics, National Institutes of Health, University of the Philippines Manila, Philippines., Biwang JH; Institutes of Human Genetics, National Institutes of Health, University of the Philippines Manila, Philippines., Melegrito JB; Institutes of Human Genetics, National Institutes of Health, University of the Philippines Manila, Philippines., Deguit CDT; Institutes of Human Genetics, National Institutes of Health, University of the Philippines Manila, Philippines., Panerio CEG; Institutes of Human Genetics, National Institutes of Health, University of the Philippines Manila, Philippines.
Jazyk: angličtina
Zdroj: Journal of the Endocrine Society [J Endocr Soc] 2022 Jun 29; Vol. 6 (8), pp. bvac092. Date of Electronic Publication: 2022 Jun 29 (Print Publication: 2022).
DOI: 10.1210/jendso/bvac092
Abstrakt: 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.
(© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)
Databáze: MEDLINE
Externí odkaz: