The MTNR1B rs10830963 variant in interaction with pre-pregnancy BMI is a pharmacogenetic marker for the initiation of antenatal insulin therapy in gestational diabetes mellitus

Gábor Firneisz, Klara Rosta, Zahra Al-Aissa, Orsolya Hadarits, Jürgen Harreiter, Ákos Nádasdi, Dagmar Bancher-Todesca, László Németh, Péter Igaz, János Rigó, István Sziller, Alexandra Kautzky-Willer, Anikó Somogyi

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The rs10830963 variant of the Melatonin Receptor 1B (MTNR1B) gene is associated with the development of gestational diabetes mellitus (GDM). We hypothesized that carrying the rs10830963/G risk allele had effect on antenatal insulin therapy (AIT) initiation in GDM in a body mass index (BMI)-dependent manner. Design: In this post hoc analysis the MTNR1B rs10830963 genotype and the clinical data of 211 Caucasian GDM patients were assessed. As a first step, a pre-pregnancy BMI threshold was determined where the effect of MTNR1B rs10830963/G allele carrying on AIT initiation was the most significant using logistic regression. Maternal age adjusted real-life odds ratios (OR) values were calculated. The chi-square test was also used to calculate the p value and 10.000 bootstrap simulations were performed in each case to re-assess the statistical power and the OR. Carrying the MTNR1B rs10830963/G allele increased the odds of AIT initiation (OR = 5.2, p = 0.02 [χ2 test], statistical power = 0.53) in GDM patients with pre-pregnancy BMI ≥ 29 kg/m2. The statistical power reached 0.77, when the pre-pregnancy BMI cutoff of 27 kg/m2 was used and the genetic effect on AIT initiation was still significant, but only using the logistic regression model. Carrying the MTNR1B rs10830963/G risk allele—in interaction with pre-pregnancy BMI—is likely be considered as a candidate pharmacogenetic marker of antenatal insulin therapy initiation and should be further assessed in precision medicine trials in GDM.

Original languageEnglish
Article number3734
JournalInternational journal of molecular sciences
Volume19
Issue number12
DOIs
Publication statusPublished - Dec 2018

Keywords

  • AIT
  • GDM
  • Gene variant
  • Genetics
  • Gestational diabetes mellitus
  • Insulin therapy
  • Lifestyle
  • MTNR1B
  • Medical nutrition therapy
  • Melatonin receptor 1B gene
  • rs10830963

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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