Haplotypes in the phospholipid transfer protein gene are associated with obesity-related phenotypes: the Québec Family Study

• Published in: International Journal of Obesity Vol. 29; no. 11; pp. 1338 - 1345
• Main Authors: BOSSE, Y, BOUCHARD, L, DESPRES, J.-P, BOUCHARD, C, PERUSSE, L, VOHL, M.-C
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 01.11.2005; Nature Publishing Group
• Subjects: Abdomen; Adipose tissue; Adult; Biological and medical sciences; Body Composition; Body fat; Body Mass Index; Chromosomes; Computed tomography; Family studies; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Genes; Genetic variance; Haplotypes; Health Surveys; Humans; Introns; Linkage Disequilibrium; Lipids; Male; Medical sciences; Metabolic diseases; Middle Aged; Mutation; Obesity; Obesity - genetics; Obesity - physiopathology; Phenotype; Phospholipid Transfer Proteins - genetics; Physiology; Polymorphism, Single Nucleotide; Proteins; Quebec; Research centers; Tomography; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Weight control; Canada; North America; America; Quebec; Quebec Canada; Phospholipid transfer protein; Obesity; Nutrition; Family study; Nutrition disorder; tests of association; Metabolic diseases; FBAT; Phenotype; Association; Gene; Genetics; Haplotype; PLTP; Nutritional status
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/sj.ijo.0803010

The phospholipid transfer protein (PLTP) may play a role in body fat regulation. To investigate the association between PLTP genetic variants and obesity-related phenotypes. 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. 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. 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.