title: Polymorphisms in the SNRPN gene are associated with obesity susceptibility in a Spanish population.
abstract: BACKGROUND
  SNRPN, which codes for the RNA-binding SmN protein, is a candidate gene for Prader-Willi syndrome. One characteristic of this neuroendocrine disorder is hyperphagia resulting in extreme obesity later in life. In the present study, we aimed to assess whether variability within this gene could be implicated in obesity susceptibility.
  
  
  METHODS
  A case-control study was performed including 265 unrelated patients with nonsyndromic and early-onset severe obesity, belonging to high-risk obesity families from Spanish ancestry; 184 healthy control individuals were included representative of the same genetic background and sex-matched. Forty-nine single nucleotide polymorphisms (SNPs) spanning the entire SNRPN gene were selected and genotyped using the Sequenom MassARRAY platform (Sequenom Inc., San Diego, CA, USA).
  
  
  RESULTS
  The four SNPs, rs12905653, rs752874, rs1391516 and rs2047433, were found to be nominally associated with obesity (p < 0.03). The diversity haplotype distribution among cases and controls identified the combination rs12905653-T/rs8028366-A/rs4028395-T as being strongly and inversely associated with obesity (odds ratio = 0.49; p = 0.0006). A genetic risk score was built based on rs12905653, rs1391516 and rs2047433 SNPs and each unit increase in genetic risk score increased the obesity risk by 49% (odds ratio = 1.49, 95% confidence interval = 1.24-1.80).
  
  
  CONCLUSIONS
  To our knowledge, this is the first study reporting an association between variability in the SNRPN gene and the risk of being obese. Interestingly, it was the major allele of each SNP that was found to be associated with the risk of weight gain. Further studies analyzing this locus and the possible additive deleterious capability of SNP combinations could be useful for demonstrating the development of obesity.
authors.affiliation: Research Center for Anthropology and Health (CIAS), University of Coimbra, Coimbra, Portugal.|Genomics Group, Fundación Investigación Hospital General Universitario de Valencia, Valencia, Spain.
authors.forename: David
authors.identifier: http://orcid.org/0000-0001-8899-9020
authors.initials: D
authors.lastname: Albuquerque
authors.affiliation: Research Center for Anthropology and Health (CIAS), University of Coimbra, Coimbra, Portugal.
authors.forename: Licínio
authors.initials: L
authors.lastname: Manco
authors.affiliation: Genomics Group, Fundación Investigación Hospital General Universitario de Valencia, Valencia, Spain.
authors.forename: Luz M
authors.initials: LM
authors.lastname: González
authors.affiliation: Department of Medical & Surgical Therapeutics, Division of Pharmacology, Medical School, University of Extremadura, Badajoz, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Gervasini
authors.affiliation: Genomics Group, Fundación Investigación Hospital General Universitario de Valencia, Valencia, Spain.|Laboratory of Molecular Genetics, Clinical Analysis Service, Hospital Universitario General de Valencia, Valencia, Spain.
authors.forename: Goitzane Marcaida
authors.initials: GM
authors.lastname: Benito
authors.affiliation: ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.|CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors.forename: Juan R
authors.initials: JR
authors.lastname: González
authors.affiliation: Genomics Group, Fundación Investigación Hospital General Universitario de Valencia, Valencia, Spain.|Laboratory of Molecular Genetics, Clinical Analysis Service, Hospital Universitario General de Valencia, Valencia, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Rodríguez-López
mesh_terms: D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D013030:Spain; D055517:snRNP Core Proteins / Q000235:genetics*
chemical_list: C526417:SNRPN protein, human; D055517:snRNP Core Proteins
keywords: BMI; SNRPN gene; Spanish population; case-control study; genetic susceptibility; obesity