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

Mireille N.M. Van Poppel*, Rosa Corcoy, David Hill, David Simmons, Leire Mendizabal, Mirella Zulueta, Laureano Simon, Gernot Desoye, DALI Core Investigator group, Dorte M. Jensen (Member of author group), Lise Lotte T. Andersen (Member of author group)

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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.

Original languageEnglish
JournalAmerican Journal of Clinical Nutrition
Volume115
Issue number2
Pages (from-to)388-396
ISSN0002-9165
DOIs
Publication statusPublished - 1. Feb 2022

Keywords

  • Gestational diabetes
  • Insulin sensitivity
  • Lifestyle intervention
  • Melatonin receptor 1B
  • Polymorphism
  • Pregnancy

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