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

Overview

Journal Diabetologia

Specialty Endocrinology

Date 2005 Jan 22

PMID 15662557

Citations 11

Authors

C F Liew

C J Groves

S Wiltshire

E Zeggini

T M Frayling

K R Owen

M Walker

G A Hitman

J C Levy

S ORahilly

A T Hattersley

D G Johnston

M I McCarthy

Affiliations

Soon will be listed here.

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.

Citing Articles

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