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

• Published in: International journal of molecular sciences 2018-11, Vol.19 (12), p.3734
• Main Authors: Firneisz, Gábor, Rosta, Klara, Al-Aissa, Zahra, Hadarits, Orsolya, Harreiter, Jürgen, Nádasdi, Ákos, Bancher-Todesca, Dagmar, Németh, László, Igaz, Péter, Rigó, Jr, János, Sziller, István, Kautzky-Willer, Alexandra, Somogyi, Anikó
• Format: Article
• Language: English
• Subjects: Adult; Alleles; Biomarkers; Blood Glucose; Body Mass Index; Body size; Chi-square test; Clinical trials; Diabetes mellitus; Diabetes, Gestational - drug therapy; Diabetes, Gestational - etiology; Diabetes, Gestational - metabolism; Female; Genetic Variation; Genotypes; Gestational diabetes; Glucose; Humans; Insulin; Insulin - therapeutic use; Markers; Melatonin; Odds Ratio; Patients; Pharmacogenetics; Pharmacology; Population; Precision medicine; Pregnancy; Receptor, Melatonin, MT2 - genetics; Statistical analysis; Statistical tests; Statistics; Treatment Outcome
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19123734

The rs10830963 variant of the ( ) gene is associated with the development of gestational diabetes mellitus (GDM). We hypothesized that carrying the rs10830963/ risk allele had effect on antenatal insulin therapy (AIT) initiation in GDM in a body mass index (BMI)-dependent manner. : In this post hoc analysis the 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 rs10830963/ 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 rs10830963/ allele increased the odds of AIT initiation (OR = 5.2, = 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 rs10830963/ 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.