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

  1. Søren K. Rasmussen1,
  2. Søren A. Urhammer1,
  3. Lars Berglund2,
  4. Jan N. Jensen1,
  5. Lars Hansen1,
  6. Søren M. Echwald1,
  7. Knut Borch-Johnsen13,
  8. Yukio Horikawa45,
  9. Hirosato Mashima4,
  10. Hans Lithell2,
  11. Nancy J. Cox67,
  12. Torben Hansen1,
  13. Graeme I. Bell4567 and
  14. Oluf Pedersen1
  1. 1Steno Diabetes Center and Hagedorn Research Institute, Gentofte, Denmark
  2. 2Department of Health and Caring Sciences/Geriatrics, University of Uppsala, Uppsala, Sweden
  3. 3Center of Preventive Medicine, Glostrup University Hospital, Glostrup, Denmark
  4. 4Department of the Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois
  5. 5Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois
  6. 6Department of Human Genetics, University of Chicago, Chicago, Illinois
  7. 7Department of Medicine, University of Chicago, Chicago, Illinois

    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.

    Footnotes

    • Address correspondence and reprint requests to Søren K. Rasmussen, PhD, Symphogen A/S, Elektrovej, Building 375, DK-2800 Lyngby, Denmark. E-mail: skr{at}symphogen.com.

      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.

    | Table of Contents