Phenotypic Differences Between Polygenic and Monogenic Hypobetalipoproteinemia.

OBJECTIVE: Primary hypobetalipoproteinemia is characterized by LDL-C (low-density lipoprotein cholesterol) concentrations below the fifth percentile. Primary hypobetalipoproteinemia mostly results from heterozygous mutations in the APOB (apolipoprotein B) and PCSK9 genes, and a polygenic origin is hypothesized in the remaining cases. Hypobetalipoproteinemia patients present an increased risk of nonalcoholic fatty liver disease and steatohepatitis. Here, we compared hepatic alterations between monogenic, polygenic, and primary hypobetalipoproteinemia of unknown cause. Approach and Results: Targeted next-generation sequencing was performed in a cohort of 111 patients with hypobetalipoproteinemia to assess monogenic and polygenic origins using an LDL-C-dedicated polygenic risk score. Forty patients (36%) had monogenic hypobetalipoproteinemia, 38 (34%) had polygenic hypobetalipoproteinemia, and 33 subjects (30%) had hypobetalipoproteinemia from an unknown cause. Patients with monogenic hypobetalipoproteinemia had lower LDL-C and apolipoprotein B plasma levels compared with those with polygenic hypobetalipoproteinemia. Liver function was assessed by hepatic ultrasonography and liver enzymes levels. Fifty-nine percent of patients with primary hypobetalipoproteinemia presented with liver steatosis, whereas 21% had increased alanine aminotransferase suggestive of liver injury. Monogenic hypobetalipoproteinemia was also associated with an increased prevalence of liver steatosis (81% versus 29%, P<0.001) and liver injury (47% versus 0%) compared with polygenic hypobetalipoproteinemia. CONCLUSIONS: This study highlights the importance of genetic diagnosis in the clinical care of primary hypobetalipoproteinemia patients. It shows for the first time that a polygenic origin of hypobetalipoproteinemia is associated with a lower risk of liver steatosis and liver injury versus monogenic hypobetalipoproteinemia. Thus, polygenic risk score is a useful tool to establish a more personalized follow-up of primary hypobetalipoproteinemia patients.

Growth Trajectories of Body Mass Index during Childhood: Associated Factors and Health Outcome at Adulthood.

OBJECTIVE: To identify body mass index (BMI) trajectories from birth to age 10 years and to assess their association with child and parental characteristics and with adult nutritional status and metabolic risk factors. STUDY DESIGN: Retrospective cohort study with 1188 subjects aged 20-60 years. Childhood growth was assessed using measured weight and height data collected retrospectively from health booklets, which also provided information on gestational age, birth weight, and early nutrition. Height, weight, waist circumference, fasting blood glucose, lipids profile, and blood pressure were measured at adulthood. Participants self-reported parental silhouette based on a 9-figural scale. Group-based modeling was applied to identify BMI trajectories. Associations were assessed using ANOVA and multiple logistic regression. RESULTS: Five growth trajectories following or crossing BMI percentiles emerged: stable-25th (15.3% of the sample), stable-50th (35.9%), stable-75th (28.0%), ascending-75th (19.2%), and ascending-obesity (1.6%). Overall, associated factors from early life were mother's corpulence (higher in the ascending-obesity group), gestational age (higher in the stable-50th, stable-75th, and in the ascending-obesity groups), and birth weight (higher in the ascending-obesity group) (all P < .05). Childhood trajectories were associated with adult BMI and waist circumference (higher in the stable-75th and in the ascending groups) (all P < .0001). CONCLUSIONS: This study shows heterogeneity in patterns of growth trajectories. Specific trajectories were associated with greater BMI and waist circumference during adulthood. Monitoring growth trajectories may improve chronic disease prevention.

Let's move our health! The experience of 40 physical activity motivational workshops / Bougeons notre santé ! L'expérience de 40 ateliers de motivation à l'activité physique.

Aims: To set up physical activity promotion workshops in health centres to help people with a sedentary lifestyle achieve an adequate level of physical activity. Methods: This health programme, called 'Bougeons Notre Santé' (Let's move our health) has been implemented since 2006 by four health centres in the Pays de la Loire region, in France. This article describes implementation of the programme, its feasibility, how it can be integrated into a global preventive approach and its outcomes on promoting more physical activity. The "Let's move our health!" programme comprises four group meetings with participants over a period of several months. At these meetings, participants discuss, exchange and monitor their qualitative and quantitative level of physical activity. Realistic and achievable goals are set in consultation with each participant in relation to their personal circumstances and are monitored with a pedometer and a follow-up diary. Support on healthy eating is also provided. This programme is an opportunity to promote health and refer participants to existing local resources. Results: Forty groups, comprising a total of 275 people, have participated in the programme since 2006. After the four meetings, participants had increased their physical activity level by an average of 723 steps per day and 85% reported that they had changed their eating habits. Conclusion: This health promotion programme is feasible and effective: an increase in the physical activity of participants was observed, together with a favourable impact on perceived health, well-being and social links. These workshops are integrated into a network of associations and institutional partners and could be implemented by similar social or health organisations.