title: Analysis of the contribution to type 2 diabetes susceptibility of sequence variation in the gene encoding stearoyl-CoA desaturase, a key regulator of lipid and carbohydrate metabolism.
abstract: OBJECTIVE
  Stearoyl-CoA desaturase (SCD) is emerging as a key regulator of lipid and carbohydrate metabolism. Scd-null mice display a beneficial metabolic phenotype characterised by resistance to obesity, diabetes and hyperlipidaemia. The human homologue, SCD, maps to a region of chromosome 10 linked to type 2 diabetes, and SCD activity correlates with insulin sensitivity. Given this strong positional and biological candidacy, the present study sought to establish whether sequence variation in SCD influences susceptibility to type 2 diabetes and related traits.
  
  
  METHODS
  The SCD gene was resequenced in 23 diabetic subjects. Six variants within coding and adjacent sequence, including a non-synonymous SNP in exon 5 (M224L), were selected for genotyping in a primary set of 608 diabetic subjects and 600 control subjects.
  
  
  RESULTS
  There was no association (at the allele, genotype or haplotype level) with type 2 diabetes, although genotype frequencies at the +14301 A>C SNP in the 3' untranslated region showed borderline association (p~0.06) when evidence for linkage was taken into account. However, replication studies (350 young-onset diabetic patients; 747 controls) failed to confirm any relationship with diabetes for this variant. No significant associations were seen for diabetes-related traits including BMI and waist-to-hip ratio.
  
  
  CONCLUSIONS
  The present study, the first reported analysis of this gene, indicates that the SCD variants typed do not explain chromosome-10-encoded susceptibility to type 2 diabetes. Although this study provided no evidence that SCD sequence variation influences diabetes susceptibility or related traits, SCD remains a major target for pharmaceutical and/or environmental manipulation.
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Old Road, Oxford, OX3 7LJ, UK.
authors.forename: C F
authors.initials: CF
authors.lastname: Liew
authors.forename: C J
authors.initials: CJ
authors.lastname: Groves
authors.forename: S
authors.initials: S
authors.lastname: Wiltshire
authors.forename: E
authors.initials: E
authors.lastname: Zeggini
authors.forename: T M
authors.initials: TM
authors.lastname: Frayling
authors.forename: K R
authors.initials: KR
authors.lastname: Owen
authors.forename: M
authors.initials: M
authors.lastname: Walker
authors.forename: G A
authors.initials: GA
authors.lastname: Hitman
authors.forename: J C
authors.initials: JC
authors.lastname: Levy
authors.forename: S
authors.initials: S
authors.lastname: O'rahilly
authors.forename: A T
authors.initials: AT
authors.lastname: Hattersley
authors.forename: D G
authors.initials: DG
authors.lastname: Johnston
authors.forename: M I
authors.initials: MI
authors.lastname: McCarthy
mesh_terms: D000328:Adult; D050260:Carbohydrate Metabolism; D002241:Carbohydrates; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007438:Introns / Q000235:genetics; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D013230:Stearoyl-CoA Desaturase / Q000235:genetics*
chemical_list: D002241:Carbohydrates; D013230:Stearoyl-CoA Desaturase