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.
|
Authors | Gábor Firneisz, Klara Rosta, Zahra Al-Aissa, Orsolya Hadarits, Jürgen Harreiter, Ákos Nádasdi, Dagmar Bancher-Todesca, László Németh, Péter Igaz, János Rigó Jr, István Sziller, Alexandra Kautzky-Willer, Anikó Somogyi |
Journal | International journal of molecular sciences
(Int J Mol Sci)
Vol. 19
Issue 12
(Nov 23 2018)
ISSN: 1422-0067 [Electronic] Switzerland |
PMID | 30477160
(Publication Type: Journal Article)
|
Chemical References |
- Biomarkers
- Blood Glucose
- Insulin
- MTNR1B protein, human
- Receptor, Melatonin, MT2
|
Topics |
- Adult
- Alleles
- Biomarkers
- Blood Glucose
- Body Mass Index
- Diabetes, Gestational
(drug therapy, etiology, metabolism)
- Female
- Genetic Variation
- Humans
- Insulin
(therapeutic use)
- Odds Ratio
- Pharmacogenetics
- Pregnancy
- Receptor, Melatonin, MT2
(genetics)
- Treatment Outcome
|