Mexican Carriers of the <i>HNF1A</i> p.E508K Variant Do Not Experience an Enhanced Response to Sulfonylureas

Martagón, Alexandro J.; Bello‐Chavolla, Omar Yaxmehen; Arellano-Campos, Olimpia; Almeda‐Valdés, Paloma; Walford, Geoffrey; Cruz-Bautista, Ivette; Gómez‐Velasco, Donají; Mehta, Roopa; Muñóz-Hernández, Liliana; Sevilla-González, Magdalena del Rocío; Viveros-Ruiz, Tannia Leticia; Ordóñez-Sánchez, María Luisa; Rodríguez‐Guillén, Rosario; Florez, José C.; Tusié-Luna, Marı́a Teresa; Aguilar-Salinas, Carlos A.

doi:10.2337/dc18-0384

Cited by 19 publications

(7 citation statements)

References 19 publications

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“…Notably, a study on the short-term response to the sulphonylurea glipizide showed that neither non-diabetic nor diabetic carriers of the Mexican/US Latino HNF1A E508K variant were sensitive to sulphonylurea stimulation. 75 Genome-wide meta-analysis also does not implicate any common HNF1A variants in the glycemic response to sulphonylurea treatment. 76 Whether carriers of the c.1108G>T variant could benefit from treatment with sulphonylurea should be pursued within the context of a randomised clinical trial establishing both short and long-term efficacy of sulphonylurea in these patients.…”

Section: Discussionmentioning

confidence: 99%

A novel splice-affecting HNF1A variant with large population impact on diabetes in Greenland

Thuesen

Stæger²,

Kaci³

et al. 2023

The Lancet Regional Health - Europe

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Section: Discussionmentioning

confidence: 99%

A novel splice-affecting HNF1A variant with large population impact on diabetes in Greenland

Thuesen

Stæger²,

Kaci³

et al. 2023

The Lancet Regional Health - Europe

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“…Patients with p.His126Asp do not respond to sulfonylureas (low and high doses), dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), or glucagon-like peptide-1 receptor agonists (GLP-1Raa), also known as incretin analogs ( 75 ). Low-dose sulfonylurea therapy is the first-line therapy for MODY3 but does not show special sensitivity to HNF1α-related T2D ( 76 ). For example, Mexican carriers of the HNF1α p.E508K variant have no increased sensitivity to sulfonylureas ( 76 ).…”

Section: Association Between Hnf1a Polymorphism and Mody3mentioning

confidence: 99%

“…Low-dose sulfonylurea therapy is the first-line therapy for MODY3 but does not show special sensitivity to HNF1α-related T2D ( 76 ). For example, Mexican carriers of the HNF1α p.E508K variant have no increased sensitivity to sulfonylureas ( 76 ).…”

Section: Association Between Hnf1a Polymorphism and Mody3mentioning

confidence: 99%

HNF1A：From Monogenic Diabetes to Type 2 Diabetes and Gestational Diabetes Mellitus

Jiang

Sun

2022

Front. Endocrinol.

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Diabetes, a disease characterized by hyperglycemia, has a serious impact on the lives and families of patients as well as on society. Diabetes is a group of highly heterogeneous metabolic diseases that can be classified as type 1 diabetes (T1D), type 2 diabetes (T2D), gestational diabetes mellitus (GDM), or other according to the etiology. The clinical manifestations are more or less similar among the different types of diabetes, and each type is highly heterogeneous due to different pathogenic factors. Therefore, distinguishing between various types of diabetes and defining their subtypes are major challenges hindering the precise treatment of the disease. T2D is the main type of diabetes in humans as well as the most heterogeneous. Fortunately, some studies have shown that variants of certain genes involved in monogenic diabetes also increase the risk of T2D. We hope this finding will enable breakthroughs regarding the pathogenesis of T2D and facilitate personalized treatment of the disease by exploring the function of the signal genes involved. Hepatocyte nuclear factor 1 homeobox A (HNF1α) is widely expressed in pancreatic β cells, the liver, the intestines, and other organs. HNF1α is highly polymorphic, but lacks a mutation hot spot. Mutations can be found at any site of the gene. Some single nucleotide polymorphisms (SNPs) cause maturity-onset diabetes of the young type 3 (MODY3) while some others do not cause MODY3 but increase the susceptibility to T2D or GDM. The phenotypes of MODY3 caused by different SNPs also differ. MODY3 is among the most common types of MODY, which is a form of monogenic diabetes mellitus caused by a single gene mutation. Both T2D and GDM are multifactorial diseases caused by both genetic and environmental factors. Different types of diabetes mellitus have different clinical phenotypes and treatments. This review focuses on HNF1α gene polymorphisms, HNF1A-MODY3, HNF1A-associated T2D and GDM, and the related pathogenesis and treatment methods. We hope this review will provide a valuable reference for the precise and individualized treatment of diabetes caused by abnormal HNF1α by summarizing the clinical heterogeneity of blood glucose abnormalities caused by HNF1α mutation.

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“…A second challenge is the difficulty to evaluate the pathogenicity of genetic variants (7), for which there is also an on-going international effort to establish guidelines and provide expert variant curations in the ClinVar database (clinicalgenome.org/affiliation/50016) (8). Furthermore, the response to alternative treatment might differ between populations (9). One of the ways to address the challenge of precise diagnostics is to complement genetic screening with additional data, combining both molecular and clinical dimensions (10).…”

Section: Introductionmentioning

confidence: 99%

A systematic mapping of the genomic and proteomic variation associated with monogenic diabetes

Kuznetsova

Vasicek

Skiadopoulou

et al. 2023

Preprint

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Monogenic diabetes is characterized as a group of diseases caused by rare variants in single genes. Multiple genes have been described to be responsible for monogenic diabetes, but the information on the variants is not unified among different resources. We have developed an automated pipeline for collecting and harmonizing data on genetic variants associated with monogenic diabetes. Furthermore, we have translated variant genetic sequences into protein sequences accounting for all protein isoforms and their variants. This allows researchers to consolidate information on variant genes and proteins associated with monogenic diabetes and facilitates their study using proteomics or structural biology. Our open and flexible implementation using Jupyter notebooks enables tailoring and modifying the pipeline and its application to other rare diseases.

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Mexican Carriers of the HNF1A p.E508K Variant Do Not Experience an Enhanced Response to Sulfonylureas

Abstract: Carriers of variant p.E508K in have a reduced insulin response rather than the increased sensitivity to sulfonylureas seen in patients with MODY3.

Cited by 19 publications

References 19 publications

A novel splice-affecting HNF1A variant with large population impact on diabetes in Greenland

A novel splice-affecting HNF1A variant with large population impact on diabetes in Greenland

HNF1A：From Monogenic Diabetes to Type 2 Diabetes and Gestational Diabetes Mellitus

A systematic mapping of the genomic and proteomic variation associated with monogenic diabetes

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