ESPE Abstracts (2018) 89 RFC6.1

Allelic Variation in Key Fitness Genes is Linked with Increased Severity of Obesity in Overweight/Obese Youth

Christoph Sanera,b, Brooke E Harcourta,b,c, Markus Juonalaa,d, Kung-Ting Kaoa,b,c, Peter Houwelinga,c, Fleur Gartona,c, Kathryn N Northa,c & Matthew A Sabina,b,c

aMurdoch Children’s Research Institute, Parkville, Australia; bDepartment of Endocrinology, The Royal Children’s Hospital, Parkville, Australia; cDepartment of Paediatrics, The University of Melbourne, Parkville, Australia; dDepartment of Medicine, University of Turku and Division of Medicine, Turku, Finland

Introduction: Childhood obesity is common and is associated with type 2 diabetes mellitus and heart disease [1]. Obesity mainly arises from an imbalance between energy intake and expenditure, although some children appear to carry a genetic predisposition for weight gain. The ability to sustain physical activity and its potential for health benefits is genetically predetermined. Candidate genes for fitness and muscle strength have been shown to substantially influence muscle function and mass in response to exercise [2]. Whether variations in genetic fitness affect a child’s propensity to weight gain, in the setting of obesity, has not been investigated. We aimed to determine whether there is a genetic predisposition in some obese children that limits their muscle’s ability to train and utilise substrates effectively, thereby perhaps increasing their risk of worsening obesity.

Methods: Investigations were performed in the Childhood Overweight BioRepository of Australia (COBRA) study, Australia’s largest longitudinal overweight and obese paediatric cohort (RCH Ethics 28081)[3]. DNA for genotyping was extracted from peripheral blood mononuclear cells (n=238; Mean BMI z-score 2.45, S.D. 0.44). SNP analysis was undertaken on a unique fitness gene panel that included; ACTN3 rs1815739, CNDP1 rs2887, HIF1A rs11549465, GALNT13 rs10196189, PPARGC1A rs8192678, RPLP1_GEMIN8P1 rs4776471, CRHBP rs1715747) using iPlex chemistry on the Sequenom MassARRAY. Correlation analyses were performed between minor allele prevalence of fitness genes and BMI z-scores, body and truncal fat percentage, waist circumference, blood pressure and accelerometer data. Significance was taken as P<0.05.

Results: Genotypes associated with athleticism and fitness were less prevalent in our overweight/obese cohort than in reference population studies (e.g. 1000 genomes project). Minor allele frequency, and therefore a more pro-fitness genotype, was associated with lower body weight and decreased waist circumference in female but not male participants. Increased daily physical activity was observed in participants with pro-fitness genotypes for four key genes. Sex dependent variation was also observed in blood pressure measurements between genotypes.

Conclusion: More severely obese children are less likely to exhibit a ‘pro-fitness genotype’ and are less physically active which may confer a greater risk of further weight gain and cardio-metabolic complications.

References: 1. Koskinen J, et al.: PMID: 28862940, J Am Heart Assoc 2017. 2. North KN, et al.: PMID: 10192379, Nat Genet 1999. 3. Sabin MA, et al.: PMID: 20969745, BMC Med Res Methodol 2010.

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