Maternal and fetal genetic contribution to gestational weight gain.

BACKGROUND: Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG. PARTICIPANTS AND METHODS: A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight). RESULTS: Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10-8) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG. CONCLUSIONS: We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG.

Treatment with liraglutide may improve markers of CVD reflected by reduced levels of apoB.

Background: Dislipidaemia and increased levels of apolipoprotein B (apoB) in individuals with obesity are risk factors for development of cardiovascular disease (CVD). The aim of this study was to investigate the effect of weight loss and weight maintenance with and without liraglutide treatment on plasma lipid profiles and apoB. Methods: Fifty-eight individuals with obesity (body mass index 34.5 ± 3.0 kg/m2 [mean ± SD]) were included in this study. After 8 weeks on a very low-calorie diet (800 kcal/day), participants were randomized to weight maintenance with meal replacements with or without liraglutide (1.2 mg daily) for 1 year. Plasma samples from before and after weight loss and after 1 year of weight maintenance were subjected to nuclear magnetic resonance-based lipidomics analysis. Results: After an 8-week low-calorie diet, study participants lost 12.0 ± 2.9 kg (mean ± SD) of their body weight, which was reflected in their lipid profiles (80 out of 124 lipids changed significantly), including reduced levels of apoB, total cholesterol, free cholesterol, remnant cholesterol, triglycerides, low-density lipoprotein and very low-density lipoprotein subclasses. After 1 year of maintained weight loss, the majority of the lipids had returned to pre-weight loss levels even though weight loss was successfully maintained in both groups. Interestingly, apoB levels remained low in the liraglutide treated group (apoB change: 0.03 ± 0.02 mmol/L, p = 0.4) in contrast to an increase in the control group (apoB change: 0.06 ± 0.07 mmol/L, p = 0.02). Conclusion: An 8-week low-calorie diet, in individuals with obesity, reduced plasma levels of lipids and the atherogenic marker apoB. After 1 year of weight maintenance, only study participants treated with liraglutide maintained reduced levels of apoB, despite similar body weight maintenance. Treatment with liraglutide may therefore reduce apoB levels and thus reflect lower CVD risk. Including apoB measurements in clinical practice when monitoring patients with dislipidemia or CVD might prove to be useful.