Variation in NCB5OR: studies of relationships to type 2 diabetes, maturity-onset diabetes of the young, and gestational diabetes mellitus.
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.
Andersen
Gitte
G
Steno Diabetes Center and Hagedorn Research Institute, Niels Steensens Vej 2, NSH2.16, DK-2820 Gentofte, Denmark. gtta@steno.dk.
Wegner
Lise
L
Rose
Christian Schack
CS
Xie
Jianxin
J
Zhu
Hao
H
Larade
Kevin
K
Johansen
Anders
A
Ek
Jakob
J
Lauenborg
Jeannet
J
Drivsholm
Thomas
T
Borch-Johnsen
Knut
K
Damm
Peter
P
Hansen
Torben
T
Bunn
H Franklin
HF
Pedersen
Oluf
O
D000818:Animals; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D042966:Cytochrome-B(5) Reductase / Q000172:deficiency / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D016640:Diabetes, Gestational / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D011247:Pregnancy; D044465:White People
C488723:Ncb5or protein, mouse; D042966:Cytochrome-B(5) Reductase