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- 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.
- Authors
Liew, C. F.; Groves, C. J.; Wiltshire, S.; Zeggini, E.; Frayling, T. M.; Owen, K. R.; Walker, M.; Hitman, G. A.; Levy, J. C.; O’Rahilly, S.; Hattersley, A. T.; Johnston, D. G.; McCarthy, M. I.
- Abstract
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 (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/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.
- Subjects
TYPE 2 diabetes; GENETICS of diabetes; DIABETES; HYPERLIPIDEMIA; METABOLIC disorders; LIPID metabolism disorders
- Publication
Diabetologia, 2004, Vol 47, Issue 12, p2168
- ISSN
0012-186X
- Publication type
Article
- DOI
10.1007/s00125-004-1575-4