Polymorphisms in the Amino Acid Transporter Solute Carrier Family 6 (Neurotransmitter Transporter) Member 14 Gene Contribute to Polygenic Obesity in French Caucasians

  1. Emmanuelle Durand1,
  2. Philippe Boutin1,
  3. David Meyre1,
  4. M. Aline Charles2,
  5. Karine Clement3,
  6. Christian Dina1 and
  7. Philippe Froguel14
  1. 1Institute of Biology, CNRS-UMR8090, Pasteur Institute, Lille, France
  2. 2Institut National de la Santé et de la Recherche Médicale (INSERM), Paul Brousse Hospital, Villejuif, France
  3. 3Department of Nutrition, Paris VI University and INSERM “Avenir,” Hôtel Dieu Hospital, Paris, France
  4. 4Hammersmith Genome Centre, Genomic Medicine, Imperial College, London, U.K
  1. Address correspondence and reprint requests to Philippe Boutin, CNRS-UMR8090, Institut Pasteur de Lille, 1 Rue du Pr. Calmette, BP 447 59021 Lille, France. E-mail: Philippe.Boutin{at}mail-good.pasteur-lille.fr

Abstract

Positional candidate gene analysis of the obesity-linked chromosome Xq24 locus identified two obesity-associated single nucleotide polymorphisms (SNPs) in the membrane amino acid transporter encoding the SLC6A14 (solute carrier family 6 [neurotransmitter transporter], member 14) gene in the Finnish population. Since we previously reported a modest evidence of linkage for this region in French obese families, we analyzed these SNPs in 1,267 obese adult case and 649 lean control subjects. SNPs 20649 C>T (odds ratio 1.23, 95% CI 1.04–1.45; P = 0.013) and 22510 C>G (1.36, 1.16–1.59; P = 0.0001) were shown to be associated with obesity in the French population. In addition, pedigree disequilibrium test results showed a modest excess of both at-risk SNP alleles in affected offspring (P = 0.05 and P = 0.08 for SNPs 20649 C>T and 22510 C>G, respectively). The SNP 22510 C>G at-risk G allele was associated, both in adult women with moderate obesity and in 234 obese girls, with higher body fat and modified perception of hunger and satiety (0.003 < P < 0.06). In conclusion, these data confirm an association of the SLC6A14 gene locus with obesity.

Footnotes

  • E.D. and P.B. contributed equally to this work.

    • Accepted June 18, 2004.
    • Received April 11, 2004.
| Table of Contents