期刊论文详细信息
BMC Medical Genetics
The MAP2K5-linked SNP rs2241423 is associated with BMI and obesity in two cohorts of Swedish and Greek children
Helgi B Schiöth4  Robert Fredriksson2  Yannis Manios1  Claude Marcus5  George P Chrousos3  Anna E Ek5  George Moschonis1  Josefin A Jacobsson2  Mathias Rask-Andersen2 
[1] Department of Nutrition & Dietetics, Harokopio University of Athens, Athens, Greece;Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Uppsala SE 75124, Sweden;First Department of Pediatrics, Athens University Medical School, Aghia Sophia Children’s Hospital, Thivon and Levadias, 115 27, Goudi, Athens, Greece;Pediatrics, National Childhood Obesity Centre, Stockholm, Sweden;Department for Clinical Science, Intervention and Technology (CLINTEC), department of Pediatrics, Karolinska Institute, Karolinska University Hospital, Huddinge, B57, 141 86, Stockholm, Sweden
关键词: rs2241423;    Genetics;    Childhood obesity;    MAP2K5;    Obesity;   
Others  :  1177861
DOI  :  10.1186/1471-2350-13-36
 received in 2012-01-24, accepted in 2012-05-04,  发布年份 2012
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【 摘 要 】

Background

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. 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.

Methods

We 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.

Results

The 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.

Conclusions

rs2241423 was associated with BMI and obesity in two independent European cohorts suggesting a role for MAP2K5 in early weight regulation.

【 授权许可】

   
2012 Rask-Andersen et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, Jackson AU, Allen HL, Lindgren CM, Luan J, Magi R, et al.: Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet 2010, 42:937-948.
  • [2]Dorajoo R, Blakemore AI, Sim X, Ong RT, Ng DP, Seielstad M, Wong TY, Saw SM, Froguel P, Liu J, Tai ES: Replication of 13 obesity loci among Singaporean Chinese, Malay and Asian-Indian populations. Int J Obes (Lond) 2011, 36:159-163.
  • [3]Winkelmann J, Schormair B, Lichtner P, Ripke S, Xiong L, Jalilzadeh S, Fulda S, Putz B, Eckstein G, Hauk S, et al.: Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions. Nat Genet 2007, 39:1000-1006.
  • [4]Wesstrom J, Nilsson S, Sundstrom-Poromaa I, Ulfberg J: Health-related quality of life and restless legs syndrome among women in Sweden. Psychiatry Clin Neurosci 2010, 64:574-579.
  • [5]Gao X, Schwarzschild MA, Wang H, Ascherio A: Obesity and restless legs syndrome in men and women. Neurology 2009, 72:1255-1261.
  • [6]Kyoto Encyclopedia of Genes and Genomes. KEGG http://www.genome.jp/kegg/ webcite
  • [7]Carter EJ, Cosgrove RA, Gonzalez I, Eisemann JH, Lovett FA, Cobb LJ, Pell JM: MEK5 and ERK5 are mediators of the pro-myogenic actions of IGF-2. J Cell Sci 2009, 122:3104-3112.
  • [8]Dong F: Gutkind JS, Larner AC: Granulocyte colony-stimulating factor induces ERK5 activation, which is differentially regulated by protein-tyrosine kinases and protein kinase C. Regulation of cell proliferation and survival. J Biol Chem 2001, 276:10811-10816.
  • [9]Kato Y, Tapping RI, Huang S, Watson MH, Ulevitch RJ, Lee JD: Bmk1/Erk5 is required for cell proliferation induced by epidermal growth factor. Nature 1998, 395:713-716.
  • [10]Clark PR, Jensen TJ, Kluger MS, Morelock M, Hanidu A, Qi Z, Tatake RJ, Pober JS: MEK5 is activated by shear stress, activates ERK5 and induces KLF4 to modulate TNF responses in human dermal microvascular endothelial cells. Microcirculation 2011, 18:102-117.
  • [11]English JM, Vanderbilt CA, Xu S, Marcus S, Cobb MH: Isolation of MEK5 and differential expression of alternatively spliced forms. J Biol Chem 1995, 270:28897-28902.
  • [12]Drew BA, Burow ME, Beckman BS: MEK5/ERK5 pathway: The first fifteen years. Biochim Biophys Acta 2012, 1825:37-48.
  • [13]Arndt S, Schmidt J, Wacker E, Karrer S, Bosserhoff AK: Fussel-15, a new player in wound healing, is deregulated in keloid and localized scleroderma. Am J Pathol 2011, 178:2622-2631.
  • [14]Arndt S, Poser I, Moser M, Bosserhoff AK: Fussel-15, a novel Ski/Sno homolog protein, antagonizes BMP signaling. Mol Cell Neurosci 2007, 34:603-611.
  • [15]Mizuhara E, Nakatani T, Minaki Y, Sakamoto Y, Ono Y: Corl1, a novel neuronal lineage-specific transcriptional corepressor for the homeodomain transcription factor Lbx1. J Biol Chem 2005, 280:3645-3655.
  • [16]Jacobsson JA, Danielsson P, Svensson V, Klovins J, Gyllensten U, Marcus C, Schioth HB, Fredriksson R: Major gender difference in association of FTO gene variant among severely obese children with obesity and obesity related phenotypes. Biochem Biophys Res Commun 2008, 368:476-482.
  • [17]Jacobsson JA, Klovins J, Kapa I, Danielsson P, Svensson V, Ridderstrale M, Gyllensten U, Marcus C, Fredriksson R, Schioth HB: Novel genetic variant in FTO influences insulin levels and insulin resistance in severely obese children and adolescents. Int J Obes (Lond) 2008, 32:1730-1735.
  • [18]Cole TJ, Bellizzi MC, Flegal KM, Dietz WH: Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 2000, 320:1240-1243.
  • [19]Moschonis G, Tanagra S, Vandorou A, Kyriakou AE, Dede V, Siatitsa PE, Koumpitski A, Androutsos O, Grammatikaki E, Kantilafti M, et al.: Social, economic and demographic correlates of overweight and obesity in primary-school children: preliminary data from the Healthy Growth Study. Public Health Nutr 2010, 13:1693-1700.
  • [20]Jacobsson JA, Rask-Andersen M, Riserus U, Moschonis G, Koumpitski A, Chrousos GP, Lannfelt L, Marcus C, Gyllensten U, Schioth HB, Fredriksson R: Genetic variants near the MGAT1 gene are associated with body weight. BMI and fatty acid metabolism among adults and children, Int J Obes (Lond); 2011.
  • [21]Cole TJ: Commentary: Beware regression to the mean. BMJ 2000, 321:281.
  • [22]Tanner JM: Growth at adolescence. Blackwell Scientific, Oxford; 1955.
  • [23]Wigginton JE, Cutler DJ, Abecasis GR: A note on exact tests of Hardy-Weinberg equilibrium. Am J Hum Genet 2005, 76:887-893.
  • [24]Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC: PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007, 81:559-575.
  • [25]Barrett JC, Fry B, Maller J, Daly MJ: Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005, 21:263-265.
  • [26]Tanner J: Growth at adolescence. Blackwell, Oxford; 1962.
  • [27]Skol AD, Scott LJ, Abecasis GR, Boehnke M: Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies. Nat Genet 2006, 38:209-213.
  • [28]Silventoinen K, Rokholm B, Kaprio J, Sorensen TI: The genetic and environmental influences on childhood obesity: a systematic review of twin and adoption studies. Int J Obes (Lond) 2010, 34:29-40.
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