The HADHSC gene encoding short-chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) and type 2 diabetes susceptibility: the DAMAGE study.
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.
van Hove
Els C
EC
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.
Hansen
Torben
T
Dekker
Jacqueline M
JM
Reiling
Erwin
E
Nijpels
Giel
G
Jørgensen
Torben
T
Borch-Johnsen
Knut
K
Hamid
Yasmin H
YH
Heine
Robert J
RJ
Pedersen
Oluf
O
Maassen
J Antonie
JA
't Hart
Leen M
LM
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
D015094:3-Hydroxyacyl CoA Dehydrogenases; D006442:Glycated Hemoglobin; C108634:HSD17B10 protein, human