title: Analysis of the contribution of FTO, NPC1, ENPP1, NEGR1, GNPDA2 and MC4R genes to obesity in Mexican children.
abstract: BACKGROUND
  Recent genome wide association studies (GWAS) and previous positional linkage studies have identified more than 50 single nucleotide polymorphisms (SNPs) associated with obesity, mostly in Europeans. We aimed to assess the contribution of some of these SNPs to obesity risk and to the variation of related metabolic traits, in Mexican children.
  
  
  METHODS
  The association of six European obesity-related SNPs in or near FTO, NPC1, ENPP1, NEGR1, GNPDA2 and MC4R genes with risk of obesity was tested in 1,463 school-aged Mexican children (N(cases) = 514; N(controls) = 949). We also assessed effects of these SNPs on the variation of body mass index (BMI), fasting serum insulin levels, fasting plasma glucose levels, total cholesterol and triglyceride levels, in a subset of 1,171 nonobese Mexican children.
  
  
  RESULTS
  We found a significant effect of GNPDA2 rs10938397 on risk of obesity (odds ratio [OR] = 1.30; P = 1.34 × 10-3). Furthermore, we found nominal associations between obesity risk or BMI variation and the following SNPs: ENPP1 rs7754561, MC4R rs17782313 and NEGR1 rs2815752. Importantly, the at-risk alleles of both MC4R rs17782313 and NPC1 rs1805081 showed significant effect on increased fasting glucose levels (β = 0.36 mmol/L; P = 1.47 × 10(-3)) and decreased fasting serum insulin levels (β = -0.10 μU/mL; P = 1.21 × 10(-3)), respectively.
  
  
  CONCLUSIONS
  Our present results suggest that some obesity-associated SNPs previously reported in Europeans also associate with risk of obesity, or metabolic quantitative traits, in Mexican children. Importantly, we found new associations between MC4R and fasting glucose levels, and between NPC1 and fasting insulin levels.
authors: Departamento de Genética y Biología Molecular, Centro de Investigación yde Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, Mexico.
authors: Aurora
authors: A
authors: Mejía-Benítez
authors: Miguel
authors: M
authors: Klünder-Klünder
authors: Loic
authors: L
authors: Yengo
authors: David
authors: D
authors: Meyre
authors: Celia
authors: C
authors: Aradillas
authors: Esperanza
authors: E
authors: Cruz
authors: Elva
authors: E
authors: Pérez-Luque
authors: Juan Manuel
authors: JM
authors: Malacara
authors: Maria Eugenia
authors: ME
authors: Garay
authors: Jesús
authors: J
authors: Peralta-Romero
authors: Samuel
authors: S
authors: Flores-Huerta
authors: Jaime
authors: J
authors: García-Mena
authors: Philippe
authors: P
authors: Froguel
authors: Miguel
authors: M
authors: Cruz
authors: Amélie
authors: A
authors: Bonnefond
mesh_terms: D019747:Aldose-Ketose Isomerases / Q000235:genetics; D000483:Alleles; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D002352:Carrier Proteins / Q000235:genetics; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D058851:GPI-Linked Proteins / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008800:Mexico / Q000453:epidemiology; D000077296:Niemann-Pick C1 Protein; D009765:Obesity / Q000208:ethnology / Q000235:genetics*; D010727:Phosphoric Diester Hydrolases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D011755:Pyrophosphatases / Q000235:genetics; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics; D012307:Risk Factors
chemical_list: D002352:Carrier Proteins; D015816:Cell Adhesion Molecules, Neuronal; D058851:GPI-Linked Proteins; D047908:Intracellular Signaling Peptides and Proteins; C470072:MC4R protein, human; D008562:Membrane Glycoproteins; C485559:NEGR1 protein, human; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein; D011506:Proteins; D044105:Receptor, Melanocortin, Type 4; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; C020582:glucosamine-6-phosphate isomerase; D011755:Pyrophosphatases; D019747:Aldose-Ketose Isomerases
references: Int J Obes Relat Metab Disord. 1996 Jun;20(6):501-6
references: 8782724
references: Diabetologia. 2012 Oct;55(10):2660-2666
references: 22869321
references: Nat Genet. 2005 Aug;37(8):863-7
references: 16025115
references: Diabetologia. 2011 Jun;54(6):1350-9
references: 21369819
references: Science. 2007 Jan 12;315(5809):187; author reply 187
references: 17218510
references: Science. 2007 Jan 12;315(5809):187; author reply 187
references: 17218508
references: Pediatrics. 2007 Dec;120 Suppl 4:S164-92
references: 18055651
references: Hum Mol Genet. 2011 Jan 15;20(2):312-21
references: 21036943
references: BMC Public Health. 2010 Jun 07;10:318
references: 20529295
references: Br J Clin Pharmacol. 2009 Dec;68(6):811-29
references: 20002076
references: Diabetes. 2010 Dec;59(12):3085-9
references: 20843981
references: Obesity (Silver Spring). 2008 Oct;16(10):2296-301
references: 18719664
references: An Pediatr (Barc). 2007 May;66(5):481-90
references: 17517203
references: J Clin Endocrinol Metab. 2010 Mar;95(3):1395-403
references: 20061430
references: Nat Genet. 2012 Sep;44(9):981-90
references: 22885922
references: Science. 2007 May 11;316(5826):889-94
references: 17434869
references: Int J Obes (Lond). 2013 Feb;37(2):191-6
references: 22430306
references: PLoS Genet. 2007 Apr 27;3(4):e61
references: 17465681
references: J Hum Genet. 2009 Dec;54(12):727-31
references: 19851340
references: Nat Genet. 2008 Jun;40(6):768-75
references: 18454148
references: Nat Genet. 2010 Nov;42(11):937-48
references: 20935630
references: Nutr Rev. 2003 Apr;61(4):139-42
references: 12795448
references: Vital Health Stat 11. 2002 May;(246):1-190
references: 12043359
references: Nat Genet. 2009 Jan;41(1):25-34
references: 19079261
references: Nat Genet. 2009 Feb;41(2):157-9
references: 19151714
references: Diabetes. 1998 Oct;47(10):1643-9
references: 9753305
references: PLoS One. 2007 Sep 12;2(9):e882
references: 17849011