Interaction between rs10830962 polymorphism in MTNR1B and lifestyle intervention on maternal and neonatal outcomes : secondary analyses of the DALI lifestyle randomized controlled trial

Background: Interactions between polymorphisms of the melatonin receptor 1B (MTNR1B ) gene and lifestyle intervention for gestational diabetes have been described. Whether these are specific for physical activity or the healthy eating intervention is unknown. Objectives: The aim was to assess the interaction between MTNR1B rs10830962 and rs10830963 polymorphisms and lifestyle interventions during pregnancy. Methods: Women with a BMI (in kg/m2) of ≥29 (n = 436) received counseling on healthy eating (HE), physical activity (PA), or both. The control group received usual care. This secondary analysis had a factorial design with comparison of HE compared with no HE and PA compared with no PA. Maternal outcomes at 24-28 wk were gestational weight gain (GWG), maternal fasting glucose, insulin, insulin resistance (HOMA-IR), disposition index, and development of GDM. Neonatal outcomes were cord blood leptin and C-peptide and estimated neonatal fat percentage. The interaction between receiving either the HE or PA intervention and genotypes of both rs10830962 and rs10830963 was assessed using multilevel regression analysis. Results: GDM risk was increased in women homozygous for the G allele of rs10830962 (OR: 2.60; 95% CI: 1.34, 5.06) or rs10830963 (OR: 2.83; 95% CI: 1.24, 6.47). Significant interactions between rs10830962 and interventions were found: in women homozygous for the G allele but not in the other genotypes, the PA intervention reduced maternal fasting insulin (β: -0.16; 95% CI: -0.33, 0.02; P = 0.08) and HOMA-IR (β: -0.17; 95% CI: -0.35, 0.01; P = 0.06), and reduced cord blood leptin (β: -0.84; 95% CI: -1.42, -0.25; P = 0.01) and C-peptide (β: -0.62; 95% CI: -1.07, -0.17; P = 0.01). In heterozygous women, the HE intervention had no effect, whereas in women homozygous for the C allele, HE intervention reduced GWG (β: −1.6 kg; 95% CI: −2.4, −0.8 kg). No interactions were found. Conclusions: In women homozygous for the risk allele of MTNR1B rs10830962, GDM risk was increased and PA intervention might be more beneficial than HE intervention for reducing maternal insulin resistance, cord blood C-peptide, and cord blood leptin.