Clustering of Cardiometabolic Risk Factors, Liver Enzymes and PNPLA3 Polymorphism With Special Reference To Children
Year: 2015
Type: dissertation
Abstract: Children with clustering of cardiometabolic risk factors have an increased risk of adulthood metabolic syndrome (MetS), type 2 diabetes and cardiovascular disease.MetS has also been associated with liver fat accumulation already in children.Elevated levels of plasma alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) have been associated with liver fat accumulation.In addition to excess body fat, also genetic factors, and mainly PNPLA3 I148M polymorphism, have been found to increase the risk of liver fat accumulation not only in adults but also in children.The purpose of this thesis was to expand knowledge on the clustering of cardiometabolic risk factors in children and adults, the associations of cardiometabolic risk factors with plasma levels of ALT and GGT in children and the relationship of the I148M polymorphism in the PNPLA3 gene with plasma ALT and GGT levels in children.Data on children were from the Physical Activity and Nutrition in Children (PANIC) Study, which is an ongoing exercise and diet intervention study in a population sample of children from the city of Kuopio, Finland.Altogether 512 children 6-8 years of age participated in the baseline study and 440 of them also took part in the 2-year follow-up study.Data on adults were from a large follow-up study in middle-aged men and from baseline examinations of a large randomized controlled trial among older individuals.Factor analysis was used to derive the MetS.MetS was represented by a second-order latent variable underlying four latent variables characterized by abdominal obesity, insulin resistance, dyslipidemia and raised blood pressure in different age groups.These secondorder factors were strongly associated with a composite cardiometabolic risk score in all age groups (r=0.84-0.99)and similarly predicted type 2 diabetes, cardiovascular outcomes and mortality in middle-aged men.The risk of type 2 diabetes, myocardial infarction and cardiovascular death increased 3.7-, 1.4-, and 1.6-fold, respectively, for a 1 SD increase in the cardiometabolic risk score.Overweight or obese children had a 2.1-times higher risk of having ALT and a 4.5-times higher risk of having GGT in the highest fifth than normalweight children.Overweight PNPLA3 148M allele carriers had higher ALT levels (23.2 U/l) at baseline than other children (18.2-19.2U/l) (P=0.024 for interaction).Moreover, they had a larger increase (6.4 U/l) in ALT levels during 2-year follow-up than other children (-0.6-0.3U/l) (P=0.002 for interaction)The findings show that MetS can be described as a single entity in widely varying age groups and that the cardiometabolic risk score is a valid tool for research evaluating cardiometabolic risk in different age groups.Moreover, cardiometabolic risk score and individual risk factors were associated with high-normal plasma levels of ALT and particularly GGT in children.Furthermore, the carriers of 148M allele of the PNPLA3 rs738409 polymorphism had elevated plasma levels of ALT if they were overweight but not if they were normal weight.
Author: Anna Viitasalo
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: Suomen Kulttuurirahasto
OpenAlex ID: W2187029469