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-Johnsen13,
- Yukio Horikawa45,
- Hirosato Mashima4,
- Hans Lithell2,
- Nancy J. Cox67,
- Torben Hansen1,
- Graeme I. Bell4567 and
- Oluf Pedersen1
- 1Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Denmark
- 2Department of Health and Caring Sciences/Geriatrics, University of Uppsala, Uppsala, Sweden
- 3Center of Preventive Medicine, Glostrup University Hospital, Glostrup, Denmark
- 4Department of the Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois
- 5Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois
- 6Department of Human Genetics, University of Chicago, Chicago, Illinois
- 7Department 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.
Address correspondence and reprint requests to Søren K. Rasmussen, PhD, Symphogen A/S, Elektrovej, Building 375, DK-2800 Lyngby, Denmark. E-mail:.
Received for publication 13 March 2002 and accepted in revised form 4 September 2002.
Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org.
HOMA, homeostasis model assessment; IVGTT, intravenous glucose tolerance test; OGTT, oral glucose tolerance test; Si, insulin sensitivity index.