Heterogeneity of the Stearoyl-CoA desaturase-1 (SCD1) gene and metabolic risk factors in the EPIC-Potsdam study

PLoS One. 2012;7(11):e48338. doi: 10.1371/journal.pone.0048338. Epub 2012 Nov 6.

Abstract

Background: Stearoyl-CoA desaturase-1 (SCD1) is an enzyme involved in lipid metabolism. In mice and humans its activity has been associated with traits of the metabolic syndrome, but also with the prevention of saturated fatty acids accumulation and subsequent inflammation, whereas for liver fat content inconsistent results have been reported. Thus, variants of the gene encoding SCD1 (SCD1) could potentially modify metabolic risk factors, but few human studies have addressed this question.

Methods: In a sample of 2157 middle-aged men and women randomly drawn from the Potsdam cohort of the European Prospective Investigation into Cancer and Nutrition, we investigated the impact of 7 SCD1 tagging-single nucleotide polymorphisms (rs1502593, rs522951, rs11190480, rs3071, rs3793767, rs10883463 and rs508384) and 5 inferred haplotypes with frequency >5% describing 90.9% of the genotype combinations in our population, on triglycerides, body mass index (BMI), waist circumference (WC), glycated haemoglobin (HbA1c), high-sensitivity C-reactive protein (hs-CRP), gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT) and fetuin-A.

Results: No significant associations between any of the SNPs or haplotypes and BMI, WC, fetuin-A and hs-CRP were observed. Associations of rs10883463 with triglycerides, GGT and HbA1c as well as of rs11190480 with ALT activity, were weak and became non-significant after multiple-testing correction. Also associations of the haplotype harbouring the minor allele of rs1502593 with HbA1c levels, the haplotype harbouring the minor alleles of rs11190480 and rs508384 with activity of ALT, and the haplotype harbouring the minor alleles of rs522951, rs10883463 and rs508384 with triglyceride and HbA1C levels and GGT activities did not withstand multiple-testing correction.

Conclusion: These findings suggest that there are no associations between common variants of SCD1 or its inferred haplotypes and the investigated metabolic risk factors. However, given the results from animal models, heterogeneity of human SCD1 warrants further investigation, in particular with regard to rare variants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Cohort Studies
  • Female
  • Genetic Heterogeneity*
  • Genetic Predisposition to Disease*
  • Germany
  • Haplotypes / genetics
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Neoplasms / genetics*
  • Neoplasms / metabolism*
  • Polymorphism, Single Nucleotide / genetics
  • Risk Factors
  • Stearoyl-CoA Desaturase / genetics*

Substances

  • SCD1 protein, human
  • Stearoyl-CoA Desaturase

Grants and funding

The recruitment phase of the EPIC-Potsdam study was funded by the German Federal Ministry of Science (01 EA 9401) and the European Union (SOC 95201408 05F02). Now EPIC-Potsdam is supported by the German Cancer Aid (70-2488-Ha I) and the European Community (SOC 98 200769 05F02). Norbert Stefan is currently funded by a Heisenberg-Professorship from the Deutsche Forschungsgemeinschaft (STE1096/3-1). Maria Arregui was funded by the Plan de Promoción de la Investigación de la Universitat Jaume I 2009 (Fundación Caixa Castelló-Bancaixa, E-2009-23) during the genotyping work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.