title: Genetic variation in a member of the laminin gene family affects variation in body composition in Drosophila and humans.
abstract: BACKGROUND
  The objective of the present study was to map candidate loci influencing naturally occurring variation in triacylglycerol (TAG) storage using quantitative complementation procedures in Drosophila melanogaster. Based on our results from Drosophila, we performed a human population-based association study to investigate the effect of natural variation in LAMA5 gene on body composition in humans.
  
  
  RESULTS
  We identified four candidate genes that contributed to differences in TAG storage between two strains of D. melanogaster, including Laminin A (LanA), which is a member of the alpha subfamily of laminin chains. We confirmed the effects of this gene using a viable LanA mutant and showed that female flies homozygous for the mutation had significantly lower TAG storage, body weight, and total protein content than control flies. Drosophila LanA is closely related to human LAMA5 gene, which maps to the well-replicated obesity-linkage region on chromosome 20q13.2-q13.3. We tested for association between three common single nucleotide polymorphisms (SNPs) in the human LAMA5 gene and variation in body composition and lipid profile traits in a cohort of unrelated women of European American (EA) and African American (AA) descent. In both ethnic groups, we found that SNP rs659822 was associated with weight (EA: P = 0.008; AA: P = 0.05) and lean mass (EA: P= 0.003; AA: P = 0.03). We also found this SNP to be associated with height (P = 0.01), total fat mass (P = 0.01), and HDL-cholesterol (P = 0.003) but only in EA women. Finally, significant associations of SNP rs944895 with serum TAG levels (P = 0.02) and HDL-cholesterol (P = 0.03) were observed in AA women.
  
  
  CONCLUSIONS
  Our results suggest an evolutionarily conserved role of a member of the laminin gene family in contributing to variation in weight and body composition.
authors.affiliation: Department of Nutrition Sciences, School of Health Professions, University of Alabama at Birmingham, 3rd Avenue South, Birmingham, AL 35294-3360, USA. mdeluca2@uab.edu
authors.forename: Maria
authors.initials: M
authors.lastname: De Luca
authors.forename: Michelle Moses
authors.initials: MM
authors.lastname: Chambers
authors.forename: Krista
authors.initials: K
authors.lastname: Casazza
authors.forename: Kerry H
authors.initials: KH
authors.lastname: Lok
authors.forename: Gary R
authors.initials: GR
authors.lastname: Hunter
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Gower
authors.forename: José R
authors.initials: JR
authors.lastname: Fernández
mesh_terms: D001741:Black or African American; D000483:Alleles; D000818:Animals; D001823:Body Composition / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007797:Laminin / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D019655:Quantitative Trait, Heritable; D013045:Species Specificity; D014280:Triglycerides / Q000378:metabolism; D044465:White People
chemical_list: D007797:Laminin; D014280:Triglycerides; C097043:laminin alpha5; C084098:laminin A