Variants in the calpain-10 gene predispose to insulin resistance and elevated free fatty acid levels.
The calpain-10 gene (CAPN10) has been associated with type 2 diabetes, but information on molecular and physiological mechanisms explaining this association is limited. Here we addressed this question by studying the role of CAPN10 for phenotypes associated with type 2 diabetes and free fatty acid (...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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2002
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| _version_ | 1797078682333872128 |
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| author | Orho-Melander, M Klannemark, M Svensson, M Ridderstråle, M Lindgren, C Groop, L |
| author_facet | Orho-Melander, M Klannemark, M Svensson, M Ridderstråle, M Lindgren, C Groop, L |
| author_sort | Orho-Melander, M |
| collection | OXFORD |
| description | The calpain-10 gene (CAPN10) has been associated with type 2 diabetes, but information on molecular and physiological mechanisms explaining this association is limited. Here we addressed this question by studying the role of CAPN10 for phenotypes associated with type 2 diabetes and free fatty acid (FFA) metabolism. Among 395 type 2 diabetic patients and 298 nondiabetic control subjects from Finland, the SNP-43 allele 1 (P = 0.011), SNP-63 allele 2 (P = 0.010), and the haplotype combination SNP-44/43/19/63 1121/1121 (P = 0.028) were associated with type 2 diabetes. The SNP-43 genotypes 11 and 12 were associated with higher fasting insulin and homeostasis model assessment (HOMA) insulin resistance index among control subjects (P = 0.021 and P = 0.0076) and with elevated FFA among both control subjects (P = 0.0040) and type 2 diabetic patients (P = 0.0025). Multiple regression analysis further indicated that SNP-43 is an independent predictor of FFA levels (P = 0.0037). Among 80 genotype discordant sibling pairs, the SNP-43 allele 1 was associated with elevated fasting serum insulin and HOMA index (P = 0.013 and P = 0.0068). None of the four SNPs showed distorted transmission of alleles to patients with type 2 diabetes in a qualitative transmission disequilibrium test, including 108 trios. Because FFA and insulin resistance are known to predict type 2 diabetes, the finding that variation in the CAPN10 gene influences FFA levels and insulin resistance may provide an explanation for how the CAPN10 gene increases susceptibility to type 2 diabetes. |
| first_indexed | 2024-03-07T00:35:15Z |
| format | Journal article |
| id | oxford-uuid:812d5a03-ce14-4498-896d-f3a1d639ba8c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:35:15Z |
| publishDate | 2002 |
| record_format | dspace |
| spelling | oxford-uuid:812d5a03-ce14-4498-896d-f3a1d639ba8c2022-03-26T21:28:38ZVariants in the calpain-10 gene predispose to insulin resistance and elevated free fatty acid levels.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:812d5a03-ce14-4498-896d-f3a1d639ba8cEnglishSymplectic Elements at Oxford2002Orho-Melander, MKlannemark, MSvensson, MRidderstråle, MLindgren, CGroop, LThe calpain-10 gene (CAPN10) has been associated with type 2 diabetes, but information on molecular and physiological mechanisms explaining this association is limited. Here we addressed this question by studying the role of CAPN10 for phenotypes associated with type 2 diabetes and free fatty acid (FFA) metabolism. Among 395 type 2 diabetic patients and 298 nondiabetic control subjects from Finland, the SNP-43 allele 1 (P = 0.011), SNP-63 allele 2 (P = 0.010), and the haplotype combination SNP-44/43/19/63 1121/1121 (P = 0.028) were associated with type 2 diabetes. The SNP-43 genotypes 11 and 12 were associated with higher fasting insulin and homeostasis model assessment (HOMA) insulin resistance index among control subjects (P = 0.021 and P = 0.0076) and with elevated FFA among both control subjects (P = 0.0040) and type 2 diabetic patients (P = 0.0025). Multiple regression analysis further indicated that SNP-43 is an independent predictor of FFA levels (P = 0.0037). Among 80 genotype discordant sibling pairs, the SNP-43 allele 1 was associated with elevated fasting serum insulin and HOMA index (P = 0.013 and P = 0.0068). None of the four SNPs showed distorted transmission of alleles to patients with type 2 diabetes in a qualitative transmission disequilibrium test, including 108 trios. Because FFA and insulin resistance are known to predict type 2 diabetes, the finding that variation in the CAPN10 gene influences FFA levels and insulin resistance may provide an explanation for how the CAPN10 gene increases susceptibility to type 2 diabetes. |
| spellingShingle | Orho-Melander, M Klannemark, M Svensson, M Ridderstråle, M Lindgren, C Groop, L Variants in the calpain-10 gene predispose to insulin resistance and elevated free fatty acid levels. |
| title | Variants in the calpain-10 gene predispose to insulin resistance and elevated free fatty acid levels. |
| title_full | Variants in the calpain-10 gene predispose to insulin resistance and elevated free fatty acid levels. |
| title_fullStr | Variants in the calpain-10 gene predispose to insulin resistance and elevated free fatty acid levels. |
| title_full_unstemmed | Variants in the calpain-10 gene predispose to insulin resistance and elevated free fatty acid levels. |
| title_short | Variants in the calpain-10 gene predispose to insulin resistance and elevated free fatty acid levels. |
| title_sort | variants in the calpain 10 gene predispose to insulin resistance and elevated free fatty acid levels |
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