Identification of microsatellite markers near the human genes encoding the beta-cell ATP-sensitive K+ channel and linkage studies with NIDDM in Japanese.
ATP-sensitive K+ (KATP) channels play a key role in stimulus-secretion coupling in pancreatic beta-cells. Recent studies have shown that the beta-cell KATP channel comprises two subunits: a novel member of the inwardly rectifying K+ channel family, designated BIR and expressed at highest levels in pancreatic islets, and the sulfonylurea receptor (SUR). Moreover, the genes encoding these two proteins are adjacent to one another on human chromosome 11. Genetic factors contribute to the development of NIDDM, and it seems likely that mutations in genes encoding proteins involved in insulin secretion or action may contribute to NIDDM susceptibility. The present study examined the contribution of the linked BIR and SUR genes to the development of NIDDM. These genes were localized to the same yeast artificial chromosome as two microsatellite DNA polymorphisms, D11S902 and D11S921. These microsatellite DNA polymorphisms were typed in 140 Japanese NIDDM-affected sib pairs. There was no evidence for linkage between these markers and NIDDM, suggesting that genetic variation in the BIR and SUR genes does not play a major role in susceptibility to NIDDM in Japanese.
Diabetes Center, Tokyo Women's Medical College, Japan.
N
N
Iwasaki
M
M
Kawamura
K
K
Yamagata
N J
NJ
Cox
S
S
Karibe
H
H
Ohgawara
N
N
Inagaki
S
S
Seino
G I
GI
Bell
Y
Y
Omori
D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate / Q000378:metabolism; D001483:Base Sequence; D018244:Chromosomes, Artificial, Yeast; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D015640:Ion Channel Gating; D007564:Japan; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug / Q000235:genetics*; D064233:Sulfonylurea Receptors
D018528:ATP-Binding Cassette Transporters; D017931:DNA Primers; D005819:Genetic Markers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000255:Adenosine Triphosphate