Polymorphisms in stearoyl coa desaturase and sterol regulatory element binding protein interact with N-3 polyunsaturated fatty acid intake to modify associations with anthropometric variables and metabolic phenotypes in Yup'ik people

Mol Nutr Food Res. 2016 Dec;60(12):2642-2653. doi: 10.1002/mnfr.201600170. Epub 2016 Sep 15.


Scope: n-3 polyunsaturated fatty acid (n-3 PUFA) intake is associated with protection from obesity; however, the mechanisms of protection remain poorly characterized. The stearoyl CoA desaturase (SCD), insulin-sensitive glucose transporter (SLC2A4), and sterol regulatory element binding protein (SREBF1) genes are transcriptionally regulated by n-3 PUFA intake and harbor polymorphisms associated with obesity. The present study investigated how consumption of n-3 PUFA modifies associations between SCD, SLC2A4, and SREBF1 polymorphisms and anthropometric variables and metabolic phenotypes.

Materials and methods: Anthropometric variables and metabolic phenotypes were measured in a cross-sectional sample of Yup'ik individuals (n = 1135) and 33 polymorphisms were tested for main effects and interactions using linear models that account for familial correlations. n-3 PUFA intake was estimated using red blood cell nitrogen stable isotope ratios. SCD polymorphisms were associated with ApoA1 concentration and n-3 PUFA interactions with SCD polymorphisms were associated with reduced fasting cholesterol levels and waist-to-hip ratio. SLC2A4 polymorphisms were associated with hip circumference, high-density lipoprotein and ApoA1 concentrations. SREBF1 polymorphisms were associated with low-density lipoprotein and HOMA-IR and n-3 PUFA interactions were associated with reduced fasting insulin and HOMA-IR levels.

Conclusion: The results suggest that an individual's genotype may interact with dietary n-3 PUFAs in ways that are associated with protection from obesity-related diseases in Yup'ik people.

Keywords: Alaska Native; BMI; Gene-by-environment interactions; n-3 PUFA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Alaska / ethnology
  • Anthropometry
  • Apolipoprotein A-I / blood
  • Cholesterol / blood
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / ethnology*
  • Diabetes Mellitus, Type 2 / genetics
  • Diet
  • Fatty Acids, Omega-3 / administration & dosage*
  • Female
  • Glucose Transporter Type 4 / genetics
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Male
  • Obesity / ethnology*
  • Obesity / genetics
  • Polymorphism, Single Nucleotide*
  • Stearoyl-CoA Desaturase / genetics*
  • Sterol Regulatory Element Binding Protein 1 / genetics


  • APOA1 protein, human
  • Apolipoprotein A-I
  • Fatty Acids, Omega-3
  • Glucose Transporter Type 4
  • Glycated Hemoglobin A
  • SLC2A4 protein, human
  • SREBF1 protein, human
  • Sterol Regulatory Element Binding Protein 1
  • Cholesterol
  • Stearoyl-CoA Desaturase