Evidence for a role of LPGAT1 in influencing BMI and percent body fat in native Americans1. (16th March 2013)

• Record Type: Journal Article
• Authors: Traurig, Michael T.; Orczewska, Julieanna I.; Ortiz, Daniel J.; Bian, Li; Marinelarena, Alejandra M.; Kobes, Sayuko; Malhotra, Alka; Hanson, Robert L.; Mason, Clint C.; Knowler, William C.; Bogardus, Clifton; Baier, Leslie J.
• Is Part Of: Obesity. Volume 21:Number 1(2013:Jan.)
• Page Start: 193
• Page End: 202
• Publication Date: 2013-03-16
• Subjects: Obesity -- Periodicals; 616.398005
• DOI: 10.1002/oby.20243
• Languages: English
• ISSNs: 1930-7381

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="abs1-1" sec-type="section"> <title>Objective:</title> <p>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 <italic>lysophosphatidylglycerol acyltransferase 1</italic> (<italic>LPGAT1</italic>) 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 <italic>LPGAT1</italic> was analyzed as a candidate gene for obesity in Pima Indians.</p> </sec> <sec id="abs1-2" sec-type="section"> <title>Design and Methods:</title> <p>Variants (<italic>n</italic> = 26) located within and adjacent to <italic>LPGAT1</italic> 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.</p> </sec> <sec id="abs1-3" sec-type="section"> <title>Results:</title> <p>Variants with nominal associations with BMI in each of the two independent samples (tagged by rs112662024 and rs12058008) had associations of <italic>P</italic> = 1‐4 × 10<sup>−5</sup> in the combined sample (<italic>n</italic> = 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. <italic>In vitro</italic> functional studies provided suggestive evidence that this 27bp deletion may affect transcriptional or posttranscriptional regulation. Analysis of <italic>LPGAT1</italic> cDNA from human preadipocytes identified an additional exon whose sequence could potentially serve as a mitochondrial targeting peptide.</p> </sec> <sec id="abs1-4" sec-type="section"> <title>Conclusions:</title> <p>LPGAT1 is a novel gene that influences BMI in Native Americans.</p> </sec> </abstract>