Genome-wide scan revealed genetic loci for energy metabolism in Hispanic children and adolescents

Abstract

Objective: Genome-wide scans were conducted in search for genetic locations linked to energy expenditure and substrate oxidation in children. Design: Pedigreed data of 1030 Hispanic children and adolescents were from the Viva La Familia Study which was designed to investigate genetic and environmental risk factors for the development of obesity in Hispanic families. A respiratory calorimeter was used to measure 24-h total energy expenditure (TEE), basal metabolic rate (BMR), sleep metabolic rate (SMR), 24-h respiratory quotient (24RQ), basal metabolic respiratory quotient (BMRQ) and sleep respiratory quotient (SRQ). Protein, fat and carbohydrate oxidation (PROOX, FATOX and CHOOX, respectively) were also estimated. All participants were genotyped for 384 single tandem repeat markers spaced an average of 10 cM apart. Computer program SOLAR was used to perform the genetic linkage analyses. Results: Significant linkage for TEE was detected on chromosome 1 near marker D1S2841, with a logarithm of the odds (LOD) score of 4.0. SMR, BMRQ and PROOX were associated with loci on chromosome 18, 17 and 9, respectively, with LOD scores of 4.88, 3.17 and 4.55, respectively. A genome-wide scan of SMR per kg fat-free mass (SpFFM) peaked in the same region as SMR on chromosome 18 (LOD, 5.24). Suggestive linkage was observed for CHOOX and FATOX. Several candidate genes were found in the above chromosomal regions including leptin receptor (LEPR). Conclusion: Regions on chromosomes 1, 9, 17 and 18 harbor genes affecting variation in energy expenditure and substrate oxidation in Hispanic children and adolescents.

Association of gene coding variation and resting metabolic rate in a multi-ethnic sample of children and adults

“…Additionally, the phenotypes assessed were not entirely consistent between the two studies, with the GWAS in Viva La Familia evaluating total and sleep EE rather than the RMR phenotype considered here, though both studies made use of whole-room indirect calorimetry. Basal energy expenditure was assessed in their study [16], utilizing the same method as our RMR measure; however, this phenotype characteristic was not included in their GWAS publication.…”

“…Although energy balance is critical to the development of obesity, few studies have examined the genetic architecture of energy expenditure (EE) in genome-wide linkage scans [16–18], admixture mapping [19], or candidate gene analyses [20–24]. A single genome-wide association study (GWAS) has examined EE and related obesity phenotypes in Hispanic children [25].…”

The FTO rs9939609 and LEPR rs1137101 mothers–newborns gene polymorphisms and maternal fat mass index effects on anthropometric characteristics in newborns

“…Recent studies sustain that LEPR rs1137101 (Gln223Arg) is the most frequent one associated with obesity. [33–35] Therefore, in some particular cases, it is important to assess these genetic factors, for example in obese pregnant women, those with excessive GWG, or even those who previously had newborns with high birth weight. In the everyday medical practice both FTO and LEPR polymorphisms can be important diagnostic tools, and even prevention ones if they are assessed in pregnant women at risk for having a macrosomic newborn, or a child with increased susceptibility for developing obesity later in life.…”

Genetic determinants of cardiovascular disease in Hispanics

“…These results indicate that there is a genetic component to physical activity behaviors. Additionally, the region that was identifi ed fl anks the melanocortin 4 receptor (MC4R) candidate gene, which has been shown to infl uence CNS regulation of food intake [41]. Further understanding of the extent to which behavioral practices are mediated by genetic predisposition is paramount; it will signifi cantly contribute toward the design of intervention strategies to fi ght CVD and its related comorbidities, particularly in populations that have been underrepresented in research.…”