title: 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.
abstract: 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.
authors.affiliation: Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Denmark. skr@symphogen.com
authors.forename: Søren K
authors.initials: SK
authors.lastname: Rasmussen
authors.forename: Søren A
authors.initials: SA
authors.lastname: Urhammer
authors.forename: Lars
authors.initials: L
authors.lastname: Berglund
authors.forename: Jan N
authors.initials: JN
authors.lastname: Jensen
authors.forename: Lars
authors.initials: L
authors.lastname: Hansen
authors.forename: Søren M
authors.initials: SM
authors.lastname: Echwald
authors.forename: Knut
authors.initials: K
authors.lastname: Borch-Johnsen
authors.forename: Yukio
authors.initials: Y
authors.lastname: Horikawa
authors.forename: Hirosato
authors.initials: H
authors.lastname: Mashima
authors.forename: Hans
authors.initials: H
authors.lastname: Lithell
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.forename: Graeme I
authors.initials: GI
authors.lastname: Bell
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
mesh_terms: 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*
chemical_list: D007328:Insulin; D002154:Calpain; C415197:calpain 10; D005947:Glucose