Variation in NCB5OR: studies of relationships to type 2 diabetes, maturity-onset diabetes of the young, and gestational diabetes mellitus

TY - JOUR

T1 - Variation in NCB5OR: studies of relationships to type 2 diabetes, maturity-onset diabetes of the young, and gestational diabetes mellitus

AU - Andersen, Gitte

AU - Wegner, Lise

AU - Rose, Christian Schack

AU - Xie, Jianxin

AU - Zhu, Hao

AU - Larade, Kevin

AU - Johansen, Anders

AU - Ek, Jakob

AU - Lauenborg, Jeannet

AU - Drivsholm, Thomas

AU - Borch-Johnsen, Knut

AU - Damm, Peter

AU - Hansen, Torben

AU - Bunn, H Franklin

AU - Pedersen, Oluf

PY - 2004/11/1

Y1 - 2004/11/1

N2 - Recent data show that homozygous Ncb5or(-/-) knock-out mice present with an early-onset nonautoimmune diabetes phenotype. Furthermore, genome-wide scans have reported linkage to the chromosome 6q14.2 region close to the human NCB5OR. We therefore considered NCB5OR to be a biological and positional candidate gene and examined the coding region of NCB5OR in 120 type 2 diabetic patients and 63 patients with maturity-onset diabetes of the young using denaturing high-performance liquid chromatography. We identified a total of 22 novel nucleotide variants. Three variants [IVS5+7del(CT), Gln187Arg, and His223Arg] were genotyped in a case-control design comprising 1,246 subjects (717 type 2 diabetic patients and 529 subjects with normal glucose tolerance). In addition, four rare variants were investigated for cosegregation with diabetes in multiplex type 2 diabetic families. The IVS5+7del(CT) variant was associated with common late-onset type 2 diabetes; however, we failed to relate this variant to any diabetes-related quantitative traits among the 529 control subjects. Thus, variation in the coding region of NCB5OR is not a major contributor in the pathogenesis of nonautoimmune diabetes.

AB - Recent data show that homozygous Ncb5or(-/-) knock-out mice present with an early-onset nonautoimmune diabetes phenotype. Furthermore, genome-wide scans have reported linkage to the chromosome 6q14.2 region close to the human NCB5OR. We therefore considered NCB5OR to be a biological and positional candidate gene and examined the coding region of NCB5OR in 120 type 2 diabetic patients and 63 patients with maturity-onset diabetes of the young using denaturing high-performance liquid chromatography. We identified a total of 22 novel nucleotide variants. Three variants [IVS5+7del(CT), Gln187Arg, and His223Arg] were genotyped in a case-control design comprising 1,246 subjects (717 type 2 diabetic patients and 529 subjects with normal glucose tolerance). In addition, four rare variants were investigated for cosegregation with diabetes in multiplex type 2 diabetic families. The IVS5+7del(CT) variant was associated with common late-onset type 2 diabetes; however, we failed to relate this variant to any diabetes-related quantitative traits among the 529 control subjects. Thus, variation in the coding region of NCB5OR is not a major contributor in the pathogenesis of nonautoimmune diabetes.

KW - Animals

KW - Chromosome Mapping

KW - Chromosomes, Human, Pair 6

KW - Cytochrome-B(5) Reductase

KW - Diabetes Mellitus, Type 2

KW - Diabetes, Gestational

KW - European Continental Ancestry Group

KW - Female

KW - Genetic Variation

KW - Humans

KW - Male

KW - Mice

KW - Mice, Knockout

KW - Middle Aged

KW - Pregnancy

M3 - Journal article

C2 - 15504981

SN - 0012-1797

VL - 53

SP - 2992

EP - 2997

JO - Diabetes

JF - Diabetes

IS - 11

ER -