The HADHSC gene encoding short-chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) and type 2 diabetes susceptibility: the DAMAGE study

TY - JOUR

T1 - The HADHSC gene encoding short-chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) and type 2 diabetes susceptibility

T2 - the DAMAGE study

AU - van Hove, Els C

AU - Hansen, Torben

AU - Dekker, Jacqueline M

AU - Reiling, Erwin

AU - Nijpels, Giel

AU - Jørgensen, Torben

AU - Borch-Johnsen, Knut

AU - Hamid, Yasmin H

AU - Heine, Robert J

AU - Pedersen, Oluf

AU - Maassen, J Antonie

AU - hart, Leen M

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

KW - 3-Hydroxyacyl CoA Dehydrogenases

KW - Body Mass Index

KW - Case-Control Studies

KW - Databases, Nucleic Acid

KW - Diabetes Mellitus, Type 2

KW - Female

KW - Genetic Predisposition to Disease

KW - Glucose Tolerance Test

KW - Hemoglobin A, Glycosylated

KW - Humans

KW - Hyperinsulinism

KW - Male

KW - Middle Aged

U2 - 10.2337/db06-0414

DO - 10.2337/db06-0414

M3 - Journal article

C2 - 17065362

SN - 0012-1797

VL - 55

SP - 3193

EP - 3196

JO - Diabetes

JF - Diabetes

IS - 11

ER -