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 FirneiszKlara RostaZahra Al-AissaOrsolya HadaritsJürgen HarreiterÁkos NádasdiDagmar Bancher-TodescaLászló NémethPéter IgazJános RigóIstván SzillerAlexandra Kautzky-WillerAnikó SomogyiPublished in: International journal of molecular sciences (2018)
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.
Keyphrases
- body mass index
- preterm birth
- pregnancy outcomes
- pregnant women
- weight gain
- type diabetes
- end stage renal disease
- genome wide
- copy number
- ejection fraction
- stem cells
- chronic kidney disease
- prognostic factors
- newly diagnosed
- gestational age
- machine learning
- metabolic syndrome
- glycemic control
- peritoneal dialysis
- insulin resistance
- replacement therapy
- weight loss