Emmi Suomela1, Mervi Oikonen2, Niina Pitkänen2, Ari Ahola-Olli2, Johanna Virtanen3, Riitta Parkkola3, Eero Jokinen4, Tomi Laitinen5, Nina Hutri-Kähönen6, Mika Kähönen7, Terho Lehtimäki8, Leena Taittonen9, Päivi Tossavainen10, Antti Jula11, Britt-Marie Loo11, Vera Mikkilä12, Risto Telama13, Jorma S A Viikari14, Markus Juonala14, Olli T Raitakari15. 1. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland. Electronic address: emkasu@utu.fi. 2. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland. 3. Department of Radiology, Turku University Central Hospital, Medical Imaging Centre of Southwest Finland, Turku, Finland. 4. Department of Pediatric Cardiology, Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland. 5. Department of Clinical Physiology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland. 6. Department of Pediatrics, University of Tampere and Tampere University Hospital, Tampere, Finland. 7. Department of Clinical Physiology, Tampere University Hospital and University of Tampere, Tampere, Finland. 8. Fimlab Laboratories and Department of Clinical Chemistry, School of Medicine, University of Tampere, Tampere, Finland. 9. Vaasa Central Hospital, Vaasa, Finland and Department of Pediatrics, University of Oulu, Oulu, Finland. 10. Department of Children and Adolescents, Oulu University Hospital, PEDEGO Research Unit and Medical Research Centre Oulu, University of Oulu, Oulu, Finland. 11. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland. 12. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; Division of Nutrition, Department of Applied Chemistry and Microbiology, University of Helsinki, Helsinki, Finland. 13. LIKES-Research Centre for Sport and Health Sciences, Jyväskylä, Finland. 14. Department of Medicine, University of Turku, and Division of Medicine, Turku University Hospital, Turku, Finland. 15. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
Abstract
BACKGROUND & AIMS: Fatty liver is a potentially preventable cause of serious liver diseases. This longitudinal study aimed to identify childhood risk factors of fatty liver in adulthood in a population-based group of Finnish adults. METHODS: Study cohort included 2,042 individuals from the Cardiovascular Risk in Young Finns Study aged 3-18years at baseline in 1980. During the latest follow-up in 2011, the liver was scanned by ultrasound. In addition to physical and environmental factors related to fatty liver, we examined whether the genetic risk posed by a single nucleotide polymorphism in the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) (rs738409) strengthens prediction of adult fatty liver. RESULTS: Independent childhood predictors of adult fatty liver were small for gestational age, (odds ratio=1.71, 95% confidence interval=1.07-2.72), variant in PNPLA3 (1.63, 1.29-2.07 per one risk allele), variant in the transmembrane 6 superfamily 2 gene (TM6SF2) (1.57, 1.08-2.30), BMI (1.30, 1.07-1.59 per standard deviation) and insulin (1.25, 1.05-1.49 per standard deviation). Childhood blood pressure, physical activity, C-reactive protein, smoking, serum lipid levels or parental lifestyle factors did not predict fatty liver. Risk assessment based on childhood age, sex, BMI, insulin levels, birth weight, TM6SF2 and PNPLA3 was superior in predicting fatty liver compared with the approach using only age, sex, BMI and insulin levels (C statistics, 0.725 vs. 0.749; p=0.002). CONCLUSIONS: Childhood risk factors on the development of fatty liver were small for gestational age, high insulin and high BMI. Prediction of adult fatty liver was enhanced by taking into account genetic variants in PNPLA3 and TM6SF2 genes. LAY SUMMARY: The increase in pediatric obesity emphasizes the importance of identification of children and adolescents at high risk of fatty liver in adulthood. We used data from the longitudinal Cardiovascular Risk in Young Finns Study to examine the associations of childhood (3-18years) risk variables with fatty liver assessed in adulthood at the age of 34-49years. The findings suggest that a multifactorial approach with both lifestyle and genetic factors included would improve early identification of children with a high risk of adult fatty liver.
BACKGROUND & AIMS: Fatty liver is a potentially preventable cause of serious liver diseases. This longitudinal study aimed to identify childhood risk factors of fatty liver in adulthood in a population-based group of Finnish adults. METHODS: Study cohort included 2,042 individuals from the Cardiovascular Risk in Young Finns Study aged 3-18years at baseline in 1980. During the latest follow-up in 2011, the liver was scanned by ultrasound. In addition to physical and environmental factors related to fatty liver, we examined whether the genetic risk posed by a single nucleotide polymorphism in the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) (rs738409) strengthens prediction of adult fatty liver. RESULTS: Independent childhood predictors of adult fatty liver were small for gestational age, (odds ratio=1.71, 95% confidence interval=1.07-2.72), variant in PNPLA3 (1.63, 1.29-2.07 per one risk allele), variant in the transmembrane 6 superfamily 2 gene (TM6SF2) (1.57, 1.08-2.30), BMI (1.30, 1.07-1.59 per standard deviation) and insulin (1.25, 1.05-1.49 per standard deviation). Childhood blood pressure, physical activity, C-reactive protein, smoking, serum lipid levels or parental lifestyle factors did not predict fatty liver. Risk assessment based on childhood age, sex, BMI, insulin levels, birth weight, TM6SF2 and PNPLA3 was superior in predicting fatty liver compared with the approach using only age, sex, BMI and insulin levels (C statistics, 0.725 vs. 0.749; p=0.002). CONCLUSIONS: Childhood risk factors on the development of fatty liver were small for gestational age, high insulin and high BMI. Prediction of adult fatty liver was enhanced by taking into account genetic variants in PNPLA3 and TM6SF2 genes. LAY SUMMARY: The increase in pediatric obesity emphasizes the importance of identification of children and adolescents at high risk of fatty liver in adulthood. We used data from the longitudinal Cardiovascular Risk in Young Finns Study to examine the associations of childhood (3-18years) risk variables with fatty liver assessed in adulthood at the age of 34-49years. The findings suggest that a multifactorial approach with both lifestyle and genetic factors included would improve early identification of children with a high risk of adult fatty liver.
Authors: Fatemeh Seyednasrollah; Johanna Mäkelä; Niina Pitkänen; Markus Juonala; Nina Hutri-Kähönen; Terho Lehtimäki; Jorma Viikari; Tanika Kelly; Changwei Li; Lydia Bazzano; Laura L Elo; Olli T Raitakari Journal: Circ Cardiovasc Genet Date: 2017-06
Authors: Zachary P Fricker; Alison Pedley; Joseph M Massaro; Ramachandran S Vasan; Udo Hoffmann; Emelia J Benjamin; Michelle T Long Journal: Clin Gastroenterol Hepatol Date: 2018-11-23 Impact factor: 11.382