Common genetic variants in the FETUB locus, genetically predicted fetuin-B levels, and risk of insulin resistance in obese Chinese adults

Medicine (Baltimore). 2017 Dec;96(50):e9234. doi: 10.1097/MD.0000000000009234.


Elevated serum fetuin-B is suggested to be associated with insulin resistance, but it is unknown if this association is causal. The aim of this study was to explore the potential causal relationship between fetuin-B and insulin resistance.We used Mendelian randomization analysis by incorporating information of genetic variants in FETUB and serum fetuin-B concentrations with insulin resistance in 1148 obese Chinese adults.Common genetic variants (FETUB rs4686434, rs6785067, and rs3733159) were significantly associated with serum fetuin-B concentrations but not with insulin resistance. Higher serum fetuin-B levels were significantly associated with increased homeostasis model assessment of insulin resistance (HOMA-IR) (0.17 [95%CI: 0.01 to 0.32, P = .037] 10 mol IU L higher per SD). However, Mendelian randomization analysis using 3 single-nucleotide polymorphisms as instrumental variables did not support a significant association between genetically predicted fetuin-B levels and HOMA-IR (-0.09 [95%CI: -0.62 to 0.44, P = .738] 10 mol IU L lower per SD). The regression coefficients for measured and genetically predicted fetuin-B concentrations on HOMA-IR were significantly different (P <.001).This study suggests the association between fetuin-B and insulin resistance may not be causal. Future studies on the nongenetic determinants of serum fetuin-B concentration to assess if such unmeasured factors may confound the association between fetuin-B and insulin resistance as well as more pathway analysis for this association are warranted.

MeSH terms

  • Adult
  • Anthropometry
  • Biomarkers / blood
  • China
  • Female
  • Fetuin-B / genetics*
  • Genetic Variation*
  • Genotype
  • Humans
  • Insulin Resistance / genetics*
  • Male
  • Mendelian Randomization Analysis
  • Obesity / blood
  • Obesity / genetics*
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Surveys and Questionnaires


  • Biomarkers
  • Fetuin-B