Abstract
Several non-synonymous single-nucleotide polymorphisms (nsSNPs) have been shown to be associated with obesity. Little is known about their associations and interactions with physical activity (PA) in relation to adiposity parameters among adolescents in Malaysia. We examined whether (a) PA and (b) selected nsSNPs are associated with adiposity parameters and whether PA interacts with these nsSNPs on these outcomes in adolescents from the Malaysian Health and Adolescents Longitudinal Research Team study (n = 1,151). Body mass indices, waist-hip ratio, and percentage body fat (% BF) were obtained. PA was assessed using Physical Activity Questionnaire for Older Children (PAQ-C). Five nsSNPs were included: beta-3 adrenergic receptor (ADRB3) rs4994, FABP2 rs1799883, GHRL rs696217, MC3R rs3827103, and vitamin D receptor rs2228570, individually and as combined genetic risk score (GRS). Associations and interactions between nsSNPs and PAQ-C scores were examined using generalized linear model. PAQ-C scores were associated with % BF (β = -0.44 [95% confidence interval -0.72, -0.16], p = 0.002). The CC genotype of ADRB3 rs4994 (β = -0.16 [-0.28, -0.05], corrected p = 0.01) and AA genotype of MC3R rs3827103 (β = -0.06 [-0.12, -0.00], p = 0.02) were significantly associated with % BF compared to TT and GG genotypes, respectively. Significant interactions with PA were found between ADRB3 rs4994 (β = -0.05 [-0.10, -0.01], p = 0.02) and combined GRS (β = -0.03 [-0.04, -0.01], p = 0.01) for % BF. Higher PA score was associated with reduced % BF in Malaysian adolescents. Of the nsSNPs, ADRB3 rs4994 and MC3R rs3827103 were associated with % BF. Significant interactions with PA were found for ADRB3 rs4994 and combined GRS on % BF but not on measurements of weight or circumferences. Targeting body fat represent prospects for molecular studies and lifestyle intervention in this population.
Highlights
Childhood obesity is a cause of much concern in Malaysia, a multiethnic country in South-East Asia, as the prevalence was estimated to be the highest in the region (22% in boys and 19% in girls) [1]
Non-synonymous single-nucleotide polymorphisms have been widely studied in different diseases, while some were found to be associated with obesity in different populations. nsSNPs are singlenucleotide polymorphisms (SNPs) with single amino acid substitution in a protein sequence that may lead to missense mutation or nonsense mutation
Among the nsSNP associated with adiposity is the fatty acid-binding protein-2 (FABP2) rs1799883 whereby the amino acid substitution from alanine to threonine was associated with increased sensitivity to carbohydrates [8]
Summary
Childhood obesity is a cause of much concern in Malaysia, a multiethnic country in South-East Asia, as the prevalence was estimated to be the highest in the region (22% in boys and 19% in girls) [1]. An increased in health problems is foreseeable as the prevalence of overweight and obesity in Malaysian adults were already among the highest in the Asian region [1]. Rarer nsSNPs such as the peroxisome proliferator-activated receptor gamma (PPARG) rs1800571 with gain-of-function mutation (Pro115Gln) has been found to be possibly pathogenic for morbid obesity [16]. These nsSNPs are relevant candidates to be studied in relation to obesity in our Malaysian adolescents. Little is known about their associations and interactions with physical activity (PA) in relation to adiposity parameters among adolescents in Malaysia
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