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Diabetes 51:3561-3567, 2002
© 2002 by the American Diabetes Association, Inc.

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

Søren K. Rasmussen1, Søren A. Urhammer1, Lars Berglund2, Jan N. Jensen1, Lars Hansen1, Søren M. Echwald1, Knut Borch-Johnsen1,3, Yukio Horikawa4,5, Hirosato Mashima4, Hans Lithell2, Nancy J. Cox6,7, Torben Hansen1, Graeme I. Bell4,5,6,7, and Oluf Pedersen1

1 Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Denmark
2 Department of Health and Caring Sciences/Geriatrics, University of Uppsala, Uppsala, Sweden
3 Center of Preventive Medicine, Glostrup University Hospital, Glostrup, Denmark
4 Department of the Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois
5 Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois
6 Department of Human Genetics, University of Chicago, Chicago, Illinois
7 Department of Medicine, University of Chicago, Chicago, Illinois

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.


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