Association of variations in the FTO, SCG3 and MTMR9 genes with metabolic syndrome in a Japanese population

J Hum Genet. 2011 Sep;56(9):647-51. doi: 10.1038/jhg.2011.74. Epub 2011 Jul 28.


Metabolic syndrome is defined as a cluster of multiple risk factors, including central obesity, dyslipidemia, hypertension and impaired glucose tolerance, that increase cardiovascular disease morbidity and mortality. Genetic factors are important in the development of metabolic syndrome, as are environmental factors. However, the genetic background of metabolic syndrome is not yet fully clarified. There is evidence that obesity and obesity-related phenotypes are associated with variations in several genes, including NEGR1, SEC16B, TMEM18, ETV5, GNPDA2, BDNF, MTCH2, SH2B1, FTO, MAF, MC4R, KCTD15, SCG3, MTMR9, TFAP2B, MSRA, LYPLAL1, GCKR and FADS1. To investigate the relationship between metabolic syndrome and variations in these genes in the Japanese population, we genotyped 33 single-nucleotide polymorphisms (SNPs) in 19 genes from 1096 patients with metabolic syndrome and 581 control individuals who had no risk factors for metabolic syndrome. Four SNPs in the FTO gene were significantly related to metabolic syndrome: rs9939609 (P=0.00013), rs8050136 (P=0.00011), rs1558902 (P=6.6 × 10(-5)) and rs1421085 (P=7.4 × 10(-5)). rs3764220 in the SCG3 gene (P=0.0010) and rs2293855 in the MTMR9 gene (P=0.0015) were also significantly associated with metabolic syndrome. SNPs in the FTO, SCG3 and MTMR9 genes had no SNP × SNP epistatic effects on metabolic syndrome. Our data suggest that genetic variations in the FTO, SCG3 and MTMR9 genes independently influence the risk of metabolic syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Asian People / genetics*
  • Body Mass Index
  • Case-Control Studies
  • Chromogranins / genetics*
  • Delta-5 Fatty Acid Desaturase
  • Diabetes Mellitus / genetics
  • Dyslipidemias / genetics
  • Female
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Hypertension / genetics
  • Male
  • Metabolic Syndrome / genetics*
  • Middle Aged
  • Obesity / genetics
  • Polymorphism, Single Nucleotide / genetics*
  • Protein Tyrosine Phosphatases, Non-Receptor / genetics*
  • Proteins / genetics*


  • Chromogranins
  • Delta-5 Fatty Acid Desaturase
  • Proteins
  • SCG3 protein, human
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human
  • FADS1 protein, human
  • MTMR9 protein, human
  • Protein Tyrosine Phosphatases, Non-Receptor