Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus.
Type 2 or non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes worldwide, affecting approximately 4% of the world's adult population. It is multifactorial in origin with both genetic and environmental factors contributing to its development. A genome-wide screen for type 2 diabetes genes carried out in Mexican Americans localized a susceptibility gene, designated NIDDM1, to chromosome 2. Here we describe the positional cloning of a gene located in the NIDDM1 region that shows association with type 2 diabetes in Mexican Americans and a Northern European population from the Botnia region of Finland. This putative diabetes-susceptibility gene encodes a ubiquitously expressed member of the calpain-like cysteine protease family, calpain-10 (CAPN10). This finding suggests a novel pathway that may contribute to the development of type 2 diabetes.
Horikawa
Y
Y
Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois, USA.
Oda
N
N
Cox
N J
NJ
Li
X
X
Orho-Melander
M
M
Hara
M
M
Hinokio
Y
Y
Lindner
T H
TH
Mashima
H
H
Schwarz
P E
PE
del Bosque-Plata
L
L
Horikawa
Y
Y
Oda
Y
Y
Yoshiuchi
I
I
Colilla
S
S
Polonsky
K S
KS
Wei
S
S
Concannon
P
P
Iwasaki
N
N
Schulze
J
J
Baier
L J
LJ
Bogardus
C
C
Groop
L
L
Boerwinkle
E
E
Hanis
C L
CL
Bell
G I
GI
D000328:Adult; D000595:Amino Acid Sequence; D002154:Calpain / Q000737:chemistry / Q000235:genetics*; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D005387:Finland; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015894:Genome, Human; D006239:Haplotypes; D006801:Humans; D017058:Mexican Americans / Q000235:genetics; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D014481:United States; D044465:White People / Q000235:genetics
D005819:Genetic Markers; D002154:Calpain; C415197:calpain 10