title: The HADHSC gene encoding short-chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) and type 2 diabetes susceptibility: the DAMAGE study.
abstract: The short-chain l-3-hydroxyacyl-CoA dehydrogenase (SCHAD) protein is involved in the penultimate step of mitochondrial fatty acid oxidation. Previously, it has been shown that mutations in the corresponding gene (HADHSC) are associated with hyperinsulinism in infancy. The presumed function of the SCHAD enzyme in glucose-stimulated insulin secretion led us to the hypothesis that common variants in HADHSC on chromosome 4q22-26 might be associated with development of type 2 diabetes. In this study, we have performed a large-scale association study in four different cohorts from the Netherlands and Denmark (n = 7,365). Direct sequencing of HADHSC cDNA and databank analysis identified four tagging single nucleotide polymorphisms (SNPs) including one missense variant (P86L). Neither the SNPs nor haplotypes investigated were associated with the disease, enzyme function, or any relevant quantitative measure (all P > 0.1). The present study provides no evidence that the specific HADHSC variants or haplotypes examined do influence susceptibility to develop type 2 diabetes. We conclude that it is unlikely that variation in HADHSC plays a major role in the pathogenesis of type 2 diabetes in the examined cohorts.
authors.affiliation: Leiden University Medical Center, Department of Molecular Cell Biology, Building 2, Room R2-005, Postal Zone S1-P, P.O. Box 9600, 2300 RC Leiden, Netherlands.
authors.forename: Els C
authors.initials: EC
authors.lastname: van Hove
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Dekker
authors.forename: Erwin
authors.initials: E
authors.lastname: Reiling
authors.forename: Giel
authors.initials: G
authors.lastname: Nijpels
authors.forename: Torben
authors.initials: T
authors.lastname: Jørgensen
authors.forename: Knut
authors.initials: K
authors.lastname: Borch-Johnsen
authors.forename: Yasmin H
authors.initials: YH
authors.lastname: Hamid
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Heine
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.forename: J Antonie
authors.initials: JA
authors.lastname: Maassen
authors.forename: Leen M
authors.initials: LM
authors.lastname: 't Hart
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000235:genetics*; D015992:Body Mass Index; D016022:Case-Control Studies; D030561:Databases, Nucleic Acid; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin; D006801:Humans; D006946:Hyperinsulinism / Q000235:genetics; D008297:Male; D008875:Middle Aged
chemical_list: D015094:3-Hydroxyacyl CoA Dehydrogenases; D006442:Glycated Hemoglobin; C108634:HSD17B10 protein, human