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Evidence for a role of LPGAT1 in influencing BMI and percent body fat in Native Americans.

ABSTRACT: 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.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.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.LPGAT1 is a novel gene that influences BMI in Native Americans.

SUBMITTER: Traurig MT

PROVIDER: S-EPMC3666094 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Evidence for a role of LPGAT1 in influencing BMI and percent body fat in Native Americans.

Traurig Michael T MT Orczewska Julieanna I JI Ortiz Daniel J DJ Bian Li L Marinelarena Alejandra M AM Kobes Sayuko S Malhotra Alka A Hanson Robert L RL Mason Clint C CC Knowler William C WC Bogardus Clifton C Baier Leslie J LJ

Obesity (Silver Spring, Md.) 20130101 1

<h4>Objective</h4>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 ob ...[more]

PMID: 23505186

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Project description:BackgroundConsumption of meals bought from out-of-home sources is a suggested risk factor for obesity, but the supporting evidence is mixed.ObjectivesTo investigate the association between consumption of different types of meals and BMI or percent body fat.MethodsData were from the UK Biobank in response to a "Type of Meals Eaten" survey, which specified the sources of the meals consumed over the previous 24 h. Because direction of causality is unknown, the data were analyzed with meal choice as the dependent variable first and then BMI as the dependent variable second.ResultsThe total number of participants was 5197 (2841 women and 2356 men). Participants with higher BMI and percent body fat were more likely to report consuming takeaway and/or delivery meals, with prevalence ORs (95% CIs) of 2.12 (95% CI: 1.40, 3.22; Bonferroni P < 0.0001) for women's adjusted BMI, 1.95 (95% CI: 1.30, 2.93; Bonferroni P < 0.0001) for women's adjusted percent body fat, 1.65 (95% CI: 1.05, 2.59; Bonferroni P < 0.002) for men's adjusted BMI, and 1.41 (95% CI: 0.70, 2.84; Bonferroni P < 0.01) for men's adjusted percent body fat. As BMI and percent body fat increased, both men and women were increasingly less likely to report having consumed a home-cooked and prepared meal during the previous 24 h. Analyzing the data with BMI and percent body fat as the dependent variable showed that both unadjusted and adjusted BMI and percent body fat were higher in individuals reporting consumption of takeaway and delivery foods the previous day and lower in those consuming homecooked meals. The probability of having consumed a meal that was prepared and eaten at a restaurant and/or café was also associated with BMI and percent fat among men but not women.ConclusionsHomecooked meals were more often consumed by those with low BMI and percent body fat, whereas delivery and takeaway meals were more often eaten by individuals with higher BMI. Consumption of fast-food/café meals was not consistently associated with BMI or percent body fat. The direction of causality in these associations cannot be inferred from this cross-sectional study.

Dataset Information

Evidence for a role of LPGAT1 in influencing BMI and percent body fat in Native Americans.

Publications

Evidence for a role of LPGAT1 in influencing BMI and percent body fat in Native Americans.

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