title: Evidence for a role of LPGAT1 in influencing BMI and percent body fat in Native Americans.
abstract: OBJECTIVE
  A genome-wide association study (GWAS) was recently completed in 1120 Pima Indians to identify loci that influence BMI. Among the top 100 signals were three variants that mapped within the lysophosphatidylglycerol acyltransferase 1 (LPGAT1) gene. LPGAT1 belongs to a large family of acyltransferases, which are involved in a variety of biological processes including pathways that regulate energy homeostasis and body weight. Therefore LPGAT1 was analyzed as a candidate gene for obesity in Pima Indians.
  
  
  METHODS
  Variants (n = 26) located within and adjacent to LPGAT1 including a novel 27bp deletion in the 5'-untranslated region identified by sequencing were genotyped in a population-based sample of 3,391 full-heritage Pima Indians living in the Gila River Indian Community. Replication of selected variants was assessed in a second sample of 3,327 mixed-heritage Native Americans from the same community.
  
  
  RESULTS
  Variants with nominal associations with BMI in each of the two independent samples (tagged by rs112662024 and rs12058008) had associations of P = 1-4 × 10(-5) in the combined sample (n = 6718). A haplotype that includes the novel 27bp deletion, which does not occur in Caucasians, showed the strongest association with BMI in the full-heritage Pima Indians. In vitro functional studies provided suggestive evidence that this 27bp deletion may affect transcriptional or posttranscriptional regulation. Analysis of LPGAT1 cDNA from human preadipocytes identified an additional exon whose sequence could potentially serve as a mitochondrial targeting peptide.
  
  
  CONCLUSIONS
  LPGAT1 is a novel gene that influences BMI in Native Americans.
authors.affiliation: Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Phoenix, Arizona, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Traurig
authors.forename: Julieanna I
authors.initials: JI
authors.lastname: Orczewska
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Ortiz
authors.forename: Li
authors.initials: L
authors.lastname: Bian
authors.forename: Alejandra M
authors.initials: AM
authors.lastname: Marinelarena
authors.forename: Sayuko
authors.initials: S
authors.lastname: Kobes
authors.forename: Alka
authors.initials: A
authors.lastname: Malhotra
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hanson
authors.forename: Clint C
authors.initials: CC
authors.lastname: Mason
authors.forename: William C
authors.initials: WC
authors.lastname: Knowler
authors.forename: Clifton
authors.initials: C
authors.lastname: Bogardus
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Baier
mesh_terms: D000217:Acyltransferases / Q000235:genetics*; D000273:Adipose Tissue; D001823:Body Composition / Q000235:genetics; D015992:Body Mass Index; D001835:Body Weight; D018076:DNA, Complementary; D004734:Energy Metabolism; D005091:Exons; D005786:Gene Expression Regulation; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D007438:Introns; D008928:Mitochondria; D009765:Obesity / Q000208:ethnology / Q000235:genetics*; D010455:Peptides / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion; D015398:Signal Transduction
chemical_list: D018076:DNA, Complementary; D010455:Peptides; D000217:Acyltransferases; C496548:LPGAT1 protein, human