Polymorphisms in the gene encoding adiponectin receptor 1 are associated with insulin resistance and high liver fat

Diabetologia. 2005 Nov;48(11):2282-91. doi: 10.1007/s00125-005-1948-3. Epub 2005 Oct 5.


Aims/hypothesis: The adipokine adiponectin has insulin-sensitising, anti-atherogenic and anti-inflammatory properties. Recently, the genes for mouse and human adiponectin receptor-1 (ADIPOR1) and -2 (ADIPOR2) have been cloned. The aim of this study was to investigate whether genetic variants of the genes encoding ADIPOR1 and ADIPOR2 play a role in human metabolism.

Materials and methods: We screened ADIPOR1 and ADIPOR2 for polymorphisms and determined their association with glucose metabolism, lipid metabolism, an atherogenic lipid profile and inflammatory markers in 502 non-diabetic subjects. A subgroup participated in a longitudinal study; these subjects received diet counselling and increased their physical activity.

Results: We identified six variants of ADIPOR1 and seven variants of ADIPOR2. A single-nucleotide polymorphism (SNP) in the putative promoter region 8503 bp upstream of the translational start codon (-8503 G/A) of ADIPOR1 (frequency of allele A=0.31) was in almost complete linkage disequilibrium with another SNP (-1927 T/C) in intron 1. Subjects carrying the -8503 A and -1927 C alleles had lower insulin sensitivity, as estimated from a 75 g OGTT (p=0.04) and determined during a euglycaemic clamp (n=295, p=0.04); they also had higher HbA(1)c levels (p=0.02) and, although the difference was not statistically significant, higher liver fat (n=85, determined by proton magnetic resonance spectroscopy, p=0.056) (all p values are adjusted for age, sex and percentage of body fat). In the longitudinal study (n=45), the -8503 A and -1927 C alleles were associated with lower insulin sensitivity (p=0.03) and higher liver fat (p=0.02) at follow-up compared with the -8503 G and -1927 T alleles, independently of basal measurements, sex and baseline and follow-up percentage of body fat.

Conclusions/interpretation: The present findings suggest that the -8503 G/A SNP in the promoter or the -1927 T/C SNP in intron 1 of ADIPOR1 may affect insulin sensitivity and liver fat in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / pathology
  • Adult
  • Body Fat Distribution
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / pathology
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Germany
  • Humans
  • Insulin Resistance / genetics*
  • Introns
  • Lipids / chemistry
  • Liver / pathology*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic
  • Receptors, Adiponectin
  • Receptors, Cell Surface / genetics*


  • ADIPOR1 protein, human
  • ADIPOR2 protein, human
  • Lipids
  • Receptors, Adiponectin
  • Receptors, Cell Surface