Aims/hypothesis. 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 ( psimilar to 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/interpretation. 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.