Abstract
BackgroundRecent genome-wide association studies have identified a single nucleotide polymorphism within the last intron of MAP2K5 associated with a higher body mass index (BMI) in adults. MAP2K5 is a component of the MAPK-family intracellular signaling pathways, responding to extracellular growth factors such as brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF). In this study, we examined the association of this variant in two cohorts of children from Sweden and Greece.MethodsWe examine the association of rs2241423 to BMI in a cohort of 474 Swedish children admitted for treatment of childhood obesity and 519 children matched for gender, ethnicity and socioeconomic background from the Stockholm area, as well as a cross-sectional cohort of 2308 Greek school children (Healthy Growth Study). Children were genotyped using a predesigned TaqMan polymorphism assay. Logistic regression was used to test for an association of rs2241423 to obesity in the cohort of Swedish children. Linear regression was used to test for an association of rs2241423 to BMI z-score and phenotypic measurements of body adiposity in the cohort of Greek children. Models were adjusted for age and gender. In the cohort of Greek children the model was also adjusted for stage of pubertal development.ResultsThe minor allele of rs2241423, allele A, was associated with a protective effect against obesity in the cohort of Swedish children (p = 0.029, OR = 0.79 (95% CI: 0.64–0.98)), and with a lower BMI z-score in the cohort of Greek children (p = 0.028, β = −0.092). No association to phenotypic measurements of body fat distribution could be observed in our study.Conclusionsrs2241423 was associated with BMI and obesity in two independent European cohorts suggesting a role for MAP2K5 in early weight regulation.
Highlights
Recent genome-wide association studies have identified a single nucleotide polymorphism within the last intron of MAP2K5 associated with a higher body mass index (BMI) in adults
The strongest association to BMI was identified as the major allele of the single nucleotide polymorphism (SNP) rs2241423 located in the last intron of the MAP2K5 gene and in proximity of the gene encoding SKI family transcriptional corepressor 1 (SKOR1) (Figure 1, Additional file 1: Figure S1)
The minor allele of rs2241423 is associated with a protective effect against obesity in a cohort of Swedish children The minor allele frequency of rs2241423 was 21.5% in the obese cohort and 25.8% in the control population
Summary
Recent genome-wide association studies have identified a single nucleotide polymorphism within the last intron of MAP2K5 associated with a higher body mass index (BMI) in adults. The strongest association to BMI was identified as the major allele of the single nucleotide polymorphism (SNP) rs2241423 located in the last intron of the MAP2K5 gene and in proximity of the gene encoding SKI family transcriptional corepressor 1 (SKOR1) (Figure 1, Additional file 1: Figure S1). This locus has previously been associated with the restless legs syndrome (RLS) [3], a condition defined by an urge to move the legs often accompanied by uncomfortable or unpleasant sensations in the legs temporarily relieved during movement. Common hereditary factors between RLS and obesity have previously been suggested [5]
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