title: Heterogeneity of the Stearoyl-CoA desaturase-1 (SCD1) gene and metabolic risk factors in the EPIC-Potsdam study.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Epidemiology, German Institute of Human Nutrition (DIfE) Potsdam-Rehbruecke, Nuthetal, Germany. Maria.Arregui@dife.de
authors.forename: Maria
authors.initials: M
authors.lastname: Arregui
authors.forename: Brian
authors.initials: B
authors.lastname: Buijsse
authors.forename: Norbert
authors.initials: N
authors.lastname: Stefan
authors.forename: Dolores
authors.initials: D
authors.lastname: Corella
authors.forename: Eva
authors.initials: E
authors.lastname: Fisher
authors.forename: Romina
authors.initials: R
authors.lastname: di Giuseppe
authors.forename: Oscar
authors.initials: O
authors.lastname: Coltell
authors.forename: Sven
authors.initials: S
authors.lastname: Knüppel
authors.forename: Krasimira
authors.initials: K
authors.lastname: Aleksandrova
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Joost
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Cornelia
authors.initials: C
authors.lastname: Weikert
mesh_terms: D000368:Aged; D000818:Animals; D015331:Cohort Studies; D005260:Female; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D005858:Germany; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D013230:Stearoyl-CoA Desaturase / Q000235:genetics*
chemical_list: C523776:SCD1 protein, human; D013230:Stearoyl-CoA Desaturase