Variants within the calpain-10 gene on chromosome 2q37 (NIDDM1) and relationships to type 2 diabetes, insulin resistance, and impaired acute insulin secretion among Scandinavian Caucasians.
Variations in the calpain-10 gene (CAPN10) have been identified among Mexican-Americans, and an at-risk haplotype combination (112/121) defined by three polymorphisms, UCSNP-43, -19, and -63, confers increased risk of type 2 diabetes. Here we examine the three polymorphisms in 1,594 Scandinavian subjects, including 409 type 2 diabetic patients, 200 glucose-tolerant control subjects, 322 young healthy subjects, 206 glucose-tolerant offspring of diabetic patients, and 457 glucose-tolerant 70-year-old men. The frequency of the 112/121 combination was not significantly different in 409 type 2 diabetic subjects compared with 200 glucose-tolerant control subjects (0.06 vs. 0.05; odds ratio 1.32 [95% CI 0.58-3.30]). In glucose-tolerant subjects, neither the single-nucleotide polymorphisms individually nor the 112/121 combination were associated with alterations in plasma glucose, serum insulin, or serum C-peptide levels at fasting or during an oral glucose tolerance test, estimates of insulin sensitivity, or glucose-induced insulin secretion. In conclusion, the frequency of the 112/121 at-risk haplotype of CAPN10 is low among Scandinavians and we were unable to demonstrate significant associations between the CAPN10 variants and type 2 diabetes, insulin resistance, or impaired insulin secretion.
Rasmussen
Søren K
SK
Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Denmark. skr@symphogen.com
Urhammer
Søren A
SA
Berglund
Lars
L
Jensen
Jan N
JN
Hansen
Lars
L
Echwald
Søren M
SM
Borch-Johnsen
Knut
K
Horikawa
Yukio
Y
Mashima
Hirosato
H
Lithell
Hans
H
Cox
Nancy J
NJ
Hansen
Torben
T
Bell
Graeme I
GI
Pedersen
Oluf
O
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002154:Calpain / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D015331:Cohort Studies; D035061:Control Groups; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005947:Glucose / Q000378:metabolism; D006239:Haplotypes; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics*; D000078790:Insulin Secretion; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000502:physiology; D012537:Scandinavian and Nordic Countries; D044465:White People / Q000235:genetics*
D007328:Insulin; D002154:Calpain; C415197:calpain 10; D005947:Glucose