title: A variant in the LRRFIP1 gene is associated with adiposity and inflammation.
abstract: Inflammation is an important factor linking abdominal obesity with insulin resistance and related cardiometabolic risk. A genome-wide association study of adiposity-related traits performed in the Quebec Family Study (QFS) revealed that a single-nucleotide polymorphism (SNP) in the LRRFIP1 gene (rs11680012) was associated with abdominal adiposity (P = 4.6 × 10(-6)).
  
  
  OBJECTIVE
  The objective of this study was to assess the relationship between polymorphisms in LRRFIP1 gene and adiposity (BMI, fat mass (FM), waist circumference (WC), and computed tomography-derived areas of total, subcutaneous and visceral abdominal adipose tissue) and markers of inflammation (C-reactive protein (CRP) and interleukin-6 (IL-6)).
  
  
  METHODS
  Using Sequenom, 16 tag SNPs in the LRRFIP1 gene, capturing 78% of the genetic variation, were genotyped in 926 participants of the QFS.
  
  
  RESULTS
  Eight SNPs (rs7575941, rs3769053, rs11689421, rs3820808, rs11680012, rs3806505, rs6739130, and rs11686141) showed evidence of association with at least two adiposity phenotypes and plasma levels of one marker of inflammation. The strongest evidence of association was observed with rs11680012, which explained 1.8-3.4% of the variance in areas of abdominal adiposity and 2.0% of the variation in CRP levels. Carriers of the rare allele of rs11680012 had ≈ 30% more abdominal adiposity (P values between 2.7 × 10(-4) and 3.8 × 10(-6)) and 75% higher CRP levels (P = 1.6 × 10(-4)) than the common allele in age and sex adjusted data. Rs11680012 is a G/C SNP converting an arginine into a threonine and this amino acid substitution may potentially alter exonic splicing.
  
  
  CONCLUSIONS
  This gene may therefore represent a potential interesting target to investigate in further functional studies on adiposity and inflammation.
authors.affiliation: Institute of Nutraceuticals and Functional Foods (INAF), Quebec City, Québec, Canada.
authors.forename: Melanie
authors.initials: M
authors.lastname: Plourde
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Vohl
authors.forename: Claire
authors.initials: C
authors.lastname: Bellis
authors.forename: Melanie
authors.initials: M
authors.lastname: Carless
authors.forename: Thomas
authors.initials: T
authors.lastname: Dyer
authors.forename: Guillaume
authors.initials: G
authors.lastname: Dolley
authors.forename: André
authors.initials: A
authors.lastname: Marette
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Després
authors.forename: Claude
authors.initials: C
authors.lastname: Bouchard
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.forename: Louis
authors.initials: L
authors.lastname: Pérusse
mesh_terms: D000273:Adipose Tissue; D050154:Adiposity / Q000235:genetics*; D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000235:genetics; D005091:Exons; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics*; D018836:Inflammation Mediators / Q000097:blood*; D007333:Insulin Resistance / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000097:blood / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011792:Quebec; D016601:RNA-Binding Proteins / Q000235:genetics*; D055105:Waist Circumference / Q000235:genetics; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D015850:Interleukin-6; C114370:LRRFIP1 protein, human; D016601:RNA-Binding Proteins; D002097:C-Reactive Protein