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.

Liew, C; Groves, C; Wiltshire, S; Zeggini, E; Frayling, T; Owen, K; Walker, M; Hitman, G; Levy, J; O'rahilly, S; Hattersley, A; Johnston, D; McCarthy, M

Journal article

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:: 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.

Publication status:: Published

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APA Style

Liew, C., Groves, C., Wiltshire, S., Zeggini, E., Frayling, T., Owen, K., Walker, M., Hitman, G., Levy, J., O'rahilly, S., Hattersley, A., Johnston, D., & McCarthy, M. (2004). 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. Diabetologia, 47(12), 2168–2175.

MLA Style

Liew, C, et al. “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.” Diabetologia, vol. 47, no. 12, 2004, pp. 2168–75.

Chicago Style

Liew, C, C Groves, S Wiltshire, et al. 2004. “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.” Diabetologia 47 (12): 2168–75.
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