title: Haplotypes in the phospholipid transfer protein gene are associated with obesity-related phenotypes: the Québec Family Study.
abstract: BACKGROUND
  The phospholipid transfer protein (PLTP) may play a role in body fat regulation.
  
  
  OBJECTIVE
  To investigate the association between PLTP genetic variants and obesity-related phenotypes.
  
  
  METHODS
  Two intronic variants, one in intron 1 (c.-87G>A) and the other in intron 12 (c.1175+68T>G), were genotyped in 811 participants of the Québec Family Study. Nine obesity-related phenotypes were investigated, including body mass index (BMI), obesity (BMI> or =30 kg/m(2)), and waist circumference, percentage of fat, fat mass and fat-free mass measured by hydrostatic weighing as well as total, visceral and subcutaneous abdominal adipose tissue areas assessed by computed tomography. Single markers and haplotypes were tested for associations in family-based designs using the FBAT program.
  
  
  RESULTS
  The SNP located in intron 1 showed significant associations with obesity, BMI, waist circumference and fat-free mass (P<0.05). The low-frequency allele (A allele) was associated with higher trait values, suggesting that the transmission of this allele is associated with an increased risk of being obese. Significant associations were observed between haplotypes and obesity, waist circumference, percentage of fat and fat-free mass (P<0.05). The transmission of the AT haplotype (frequency=0.180) was positively associated with obesity-related phenotypes. After sequencing the promoter and the coding regions of the PLTP gene, we were unable to identify a mutation that could replicate these results.
  
  
  CONCLUSIONS
  Intronic variants of the PLTP gene are significantly associated with obesity-related phenotypes. Considering the number and the relevance of candidate genes surrounding the PLTP locus and the absence of missense polymorphisms in the coding region, the associations could be mediated by a second gene allele in linkage disequilibrium with the marker locus.
authors.affiliation: Lipid Research Center, CHUL Research Center, Laval University, Québec, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Bossé
authors.forename: L
authors.initials: L
authors.lastname: Bouchard
authors.forename: J-P
authors.initials: JP
authors.lastname: Després
authors.forename: C
authors.initials: C
authors.lastname: Bouchard
authors.forename: L
authors.initials: L
authors.lastname: Pérusse
authors.forename: M-C
authors.initials: MC
authors.lastname: Vohl
mesh_terms: D000328:Adult; D001823:Body Composition; D015992:Body Mass Index; D005260:Female; D006239:Haplotypes; D006306:Health Surveys; D006801:Humans; D007438:Introns; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D049294:Phospholipid Transfer Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011792:Quebec
chemical_list: D049294:Phospholipid Transfer Proteins