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Variants in the calpain-10 gene predispose to insulin resistance and elevated free fatty acid levels.

Orho-Melander, Marju LU ; Klannemark, Mia LU ; Svensson, Malin LU ; Ridderstråle, Martin LU ; Lindgren, Cecilia LU and Groop, Leif LU (2002) In Diabetes 51(8). p.2658-2664
Abstract
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... (More)
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. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
keywords
Middle Age, Support, Insulin Resistance : genetics, Insulin : blood, Human, Haplotypes, Genotype, Finland, Female, Nonesterified : blood, Case-Control Studies, Fatty Acids, Male, Non-U.S. Gov't, Calpain : genetics, Body Constitution, Blood Glucose : metabolism, Alleles
in
Diabetes
volume
51
issue
8
pages
2658 - 2664
publisher
American Diabetes Association Inc.
external identifiers
  • pmid:12145185
  • wos:000177185900043
  • scopus:0036321080
ISSN
1939-327X
DOI
10.2337/diabetes.51.8.2658
language
English
LU publication?
yes
id
9b48de96-351d-40f4-9322-cc019c87b7f7 (old id 109647)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12145185&dopt=Abstract
date added to LUP
2007-07-27 14:27:04
date last changed
2017-07-23 04:45:04
@article{9b48de96-351d-40f4-9322-cc019c87b7f7,
  abstract     = {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.},
  author       = {Orho-Melander, Marju and Klannemark, Mia and Svensson, Malin and Ridderstråle, Martin and Lindgren, Cecilia and Groop, Leif},
  issn         = {1939-327X},
  keyword      = {Middle Age,Support,Insulin Resistance : genetics,Insulin : blood,Human,Haplotypes,Genotype,Finland,Female,Nonesterified : blood,Case-Control Studies,Fatty Acids,Male,Non-U.S. Gov't,Calpain : genetics,Body Constitution,Blood Glucose : metabolism,Alleles},
  language     = {eng},
  number       = {8},
  pages        = {2658--2664},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Variants in the calpain-10 gene predispose to insulin resistance and elevated free fatty acid levels.},
  url          = {http://dx.doi.org/10.2337/diabetes.51.8.2658},
  volume       = {51},
  year         = {2002},
}