A missense variant in GLP1R gene is associated with the glycaemic response to treatment with gliptins

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F16%3A10328169" target="_blank" >RIV/00064203:_____/16:10328169 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/16:10328169

Výsledek na webu

<a href="http://dx.doi.org/10.1111/dom.12682" target="_blank" >http://dx.doi.org/10.1111/dom.12682</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/dom.12682" target="_blank" >10.1111/dom.12682</a>

Jazyk výsledku

angličtina

Název v původním jazyce

A missense variant in GLP1R gene is associated with the glycaemic response to treatment with gliptins

Popis výsledku v původním jazyce

Gliptins act by increasing endogenous incretin levels. Glucagon-like peptide-1 receptor (GLP1R) and glucose-dependent insulinotropic peptide receptor (GIPR) are their indirect drug targets. Variants of GLP1R and GIPR have previously been associated with the incretin effect. The aim of the present pilot study was to examine associations of the GLP1R and GIPR gene variants with the glycaemic response to gliptins. A total of 140 consecutive patients with type 2 diabetes were followed-up 6 months after initiation of gliptin treatment. GLP1R rs6923761 (Gly168Ser) and GIPR rs10423928 genotyping was performed using real-time PCR, with subsequent high-resolution melting analysis. The main study outcome was reduction in glycated haemoglobin (HbA1c) after treatment. GLP1R Gly168Ser variant was significantly associated with reduction in HbA1c in an additive model (beta = -0.33, p = 0.011). The mean reduction in HbA1c in Ser/Ser homozygotes was significantly lower compared with Gly-allele carriers [0.12 +/- 0.23% vs. 0.80 +/- 0.09% (1.3 +/- 2.5 mmol/mol vs. 8.7 +/- 1.0 mmol/mol); p = 0.008]. In conclusion, GLP1R missense variant was associated with a reduced response to gliptin treatment. The genotype-related effect size of similar to 0.7% (8 mmol/mol) is equal to an average effect of gliptin treatment and makes this variant a candidate for use in precision medicine.

Název v anglickém jazyce

A missense variant in GLP1R gene is associated with the glycaemic response to treatment with gliptins

Popis výsledku anglicky

Gliptins act by increasing endogenous incretin levels. Glucagon-like peptide-1 receptor (GLP1R) and glucose-dependent insulinotropic peptide receptor (GIPR) are their indirect drug targets. Variants of GLP1R and GIPR have previously been associated with the incretin effect. The aim of the present pilot study was to examine associations of the GLP1R and GIPR gene variants with the glycaemic response to gliptins. A total of 140 consecutive patients with type 2 diabetes were followed-up 6 months after initiation of gliptin treatment. GLP1R rs6923761 (Gly168Ser) and GIPR rs10423928 genotyping was performed using real-time PCR, with subsequent high-resolution melting analysis. The main study outcome was reduction in glycated haemoglobin (HbA1c) after treatment. GLP1R Gly168Ser variant was significantly associated with reduction in HbA1c in an additive model (beta = -0.33, p = 0.011). The mean reduction in HbA1c in Ser/Ser homozygotes was significantly lower compared with Gly-allele carriers [0.12 +/- 0.23% vs. 0.80 +/- 0.09% (1.3 +/- 2.5 mmol/mol vs. 8.7 +/- 1.0 mmol/mol); p = 0.008]. In conclusion, GLP1R missense variant was associated with a reduced response to gliptin treatment. The genotype-related effect size of similar to 0.7% (8 mmol/mol) is equal to an average effect of gliptin treatment and makes this variant a candidate for use in precision medicine.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FB - Endokrinologie, diabetologie, metabolismus, výživa

OECD FORD obor

—

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Diabetes, Obesity and Metabolism

ISSN

1462-8902

e-ISSN

—

Svazek periodika

18

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

4

Strana od-do

941-944

Kód UT WoS článku

000381664000013

EID výsledku v databázi Scopus

2-s2.0-84973531881