Genotypic and phenotypic factors influencing drug response in Mexican patients with type 2 Diabetes Mellitus

Hector E. Sanchez-Ibarra, Luisa M. Reyes-Cortes, Xian Li Jiang, Claudia M. Luna-Aguirre, Dionicio Aguirre-Trevino, Ivan A. Morales-Alvarado, Rafael B. Leon-Cachon, Fernando Lavalle-Gonzalez, Faruck Morcos, Hugo A. Barrera-Saldaña

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Abstract

The treatment of Type 2 Diabetes Mellitus (T2DM) consists primarily of oral antidiabetic drugs (OADs) that stimulate insulin secretion, such as sulfonylureas (SUs) and reduce hepatic glucose production (e.g., biguanides), among others. The marked inter-individual differences among T2DM patients' response to these drugs have become an issue on prescribing and dosing efficiently. In this study, fourteen polymorphisms selected from Genome-wide association studies (GWAS) were screened in 495 T2DM Mexican patients previously treated with OADs to find the relationship between the presence of these polymorphisms and response to the OADs. Then, a novel association screening method, based on global probabilities, was used to globally characterize important relationships between the drug response to OADs and genetic and clinical parameters, including polymorphisms, patient information, and type of treatment. Two polymorphisms, ABCC8-Ala1369Ser and KCNJ11-Glu23Lys, showed a significant impact on response to SUs. Heterozygous ABCC8-Ala1369Ser variant (A/C) carriers exhibited a higher response to SUs compared to homozygous ABCC8-Ala1369Ser variant (A/A) carriers (p-value = 0.029) and to homozygous wild-type genotypes (C/C) (p-value = 0.012). The homozygous KCNJ11-Glu23Lys variant (C/C) and wild-type (T/T) genotypes had a lower response to SUs compared to heterozygous (C/T) carriers (p-value = 0.039). The screening of OADs response related genetic and clinical factors could help improve the prescribing and dosing of OADs for T2DM patients and thus contribute to the design of personalized treatments.

Original languageEnglish
Article number320
JournalFrontiers in Pharmacology
Volume9
Issue numberAPR
DOIs
Publication statusPublished - 6 Apr 2018

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Hypoglycemic Agents
Type 2 Diabetes Mellitus
Pharmaceutical Preparations
Genotype
Biguanides
Genome-Wide Association Study
Individuality
Therapeutics
Insulin
Glucose
Liver

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Cite this

Sanchez-Ibarra, H. E., Reyes-Cortes, L. M., Jiang, X. L., Luna-Aguirre, C. M., Aguirre-Trevino, D., Morales-Alvarado, I. A., ... Barrera-Saldaña, H. A. (2018). Genotypic and phenotypic factors influencing drug response in Mexican patients with type 2 Diabetes Mellitus. Frontiers in Pharmacology, 9(APR), [320]. https://doi.org/10.3389/fphar.2018.00320
Sanchez-Ibarra, Hector E. ; Reyes-Cortes, Luisa M. ; Jiang, Xian Li ; Luna-Aguirre, Claudia M. ; Aguirre-Trevino, Dionicio ; Morales-Alvarado, Ivan A. ; Leon-Cachon, Rafael B. ; Lavalle-Gonzalez, Fernando ; Morcos, Faruck ; Barrera-Saldaña, Hugo A. / Genotypic and phenotypic factors influencing drug response in Mexican patients with type 2 Diabetes Mellitus. In: Frontiers in Pharmacology. 2018 ; Vol. 9, No. APR.
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abstract = "The treatment of Type 2 Diabetes Mellitus (T2DM) consists primarily of oral antidiabetic drugs (OADs) that stimulate insulin secretion, such as sulfonylureas (SUs) and reduce hepatic glucose production (e.g., biguanides), among others. The marked inter-individual differences among T2DM patients' response to these drugs have become an issue on prescribing and dosing efficiently. In this study, fourteen polymorphisms selected from Genome-wide association studies (GWAS) were screened in 495 T2DM Mexican patients previously treated with OADs to find the relationship between the presence of these polymorphisms and response to the OADs. Then, a novel association screening method, based on global probabilities, was used to globally characterize important relationships between the drug response to OADs and genetic and clinical parameters, including polymorphisms, patient information, and type of treatment. Two polymorphisms, ABCC8-Ala1369Ser and KCNJ11-Glu23Lys, showed a significant impact on response to SUs. Heterozygous ABCC8-Ala1369Ser variant (A/C) carriers exhibited a higher response to SUs compared to homozygous ABCC8-Ala1369Ser variant (A/A) carriers (p-value = 0.029) and to homozygous wild-type genotypes (C/C) (p-value = 0.012). The homozygous KCNJ11-Glu23Lys variant (C/C) and wild-type (T/T) genotypes had a lower response to SUs compared to heterozygous (C/T) carriers (p-value = 0.039). The screening of OADs response related genetic and clinical factors could help improve the prescribing and dosing of OADs for T2DM patients and thus contribute to the design of personalized treatments.",
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Sanchez-Ibarra, HE, Reyes-Cortes, LM, Jiang, XL, Luna-Aguirre, CM, Aguirre-Trevino, D, Morales-Alvarado, IA, Leon-Cachon, RB, Lavalle-Gonzalez, F, Morcos, F & Barrera-Saldaña, HA 2018, 'Genotypic and phenotypic factors influencing drug response in Mexican patients with type 2 Diabetes Mellitus', Frontiers in Pharmacology, vol. 9, no. APR, 320. https://doi.org/10.3389/fphar.2018.00320

Genotypic and phenotypic factors influencing drug response in Mexican patients with type 2 Diabetes Mellitus. / Sanchez-Ibarra, Hector E.; Reyes-Cortes, Luisa M.; Jiang, Xian Li; Luna-Aguirre, Claudia M.; Aguirre-Trevino, Dionicio; Morales-Alvarado, Ivan A.; Leon-Cachon, Rafael B.; Lavalle-Gonzalez, Fernando; Morcos, Faruck; Barrera-Saldaña, Hugo A.

In: Frontiers in Pharmacology, Vol. 9, No. APR, 320, 06.04.2018.

Research output: Contribution to journalArticle

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T1 - Genotypic and phenotypic factors influencing drug response in Mexican patients with type 2 Diabetes Mellitus

AU - Sanchez-Ibarra, Hector E.

AU - Reyes-Cortes, Luisa M.

AU - Jiang, Xian Li

AU - Luna-Aguirre, Claudia M.

AU - Aguirre-Trevino, Dionicio

AU - Morales-Alvarado, Ivan A.

AU - Leon-Cachon, Rafael B.

AU - Lavalle-Gonzalez, Fernando

AU - Morcos, Faruck

AU - Barrera-Saldaña, Hugo A.

PY - 2018/4/6

Y1 - 2018/4/6

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Sanchez-Ibarra HE, Reyes-Cortes LM, Jiang XL, Luna-Aguirre CM, Aguirre-Trevino D, Morales-Alvarado IA et al. Genotypic and phenotypic factors influencing drug response in Mexican patients with type 2 Diabetes Mellitus. Frontiers in Pharmacology. 2018 Apr 6;9(APR). 320. https://doi.org/10.3389/fphar.2018.00320