Association of Metabolites with Obesity and Type 2 Diabetes Based on FTO Genotype

PLoS One. 2016 Jun 1;11(6):e0156612. doi: 10.1371/journal.pone.0156612. eCollection 2016.

Abstract

The single nucleotide polymorphism rs9939609 of the gene FTO, which encodes fat mass and obesity-associated protein, is strongly associated with obesity and type 2 diabetes (T2D) in multiple populations; however, the underlying mechanism of this association is unclear. The present study aimed to investigate FTO genotype-dependent metabolic changes in obesity and T2D. To elucidate metabolic dysregulation associated with disease risk genotype, genomic and metabolomic datasets were recruited from 2,577 participants of the Korean Association REsource (KARE) cohort, including 40 homozygous carriers of the FTO risk allele (AA), 570 heterozygous carriers (AT), and 1,967 participants carrying no risk allele (TT). A total of 134 serum metabolites were quantified using a targeted metabolomics approach. Through comparison of various statistical methods, seven metabolites were identified that are significantly altered in obesity and T2D based on the FTO risk allele (adjusted p < 0.05). These identified metabolites are relevant to phosphatidylcholine metabolic pathway, and previously reported to be metabolic markers of obesity and T2D. In conclusion, using metabolomics with the information from genome-wide association studies revealed significantly altered metabolites depending on the FTO genotype in complex disorders. This study may contribute to a better understanding of the biological mechanisms linking obesity and T2D.

MeSH terms

  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO / genetics*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism*
  • Genome-Wide Association Study
  • Genotype*
  • Humans
  • Obesity / genetics
  • Obesity / metabolism*

Substances

  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human

Grants and funding

This work was supported by intramural grants from the Korea National Institute of Health (2013-NG73001-00). Biospecimens and data were obtained from the Korean Genome Analysis Project (4845-301), the Korean Genome and Epidemiology Study (4851-302), and the Korea Biobank Project (4851-307, KBP-2014-02), which are supported by the Korea Center for Disease Control and Prevention, Republic of Korea.