Variants in the calpain-10 gene predispose to insulin resistance and elevated free fatty acid levels.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/109647
- author
- Orho-Melander, Marju LU ; Klannemark, Mia LU ; Svensson, Malin LU ; Ridderstråle, Martin LU ; Lindgren, Cecilia LU and Groop, Leif LU
- organization
- publishing date
- 2002
- 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
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Diabetes and Endocrinology (013241530), Clinical Obesity (013241521), Pediatrics/Urology/Gynecology/Endocrinology (013240400)
- 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
- 2016-04-01 16:46:59
- date last changed
- 2024-02-26 23:55:16
@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}},
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}},
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}},
doi = {{10.2337/diabetes.51.8.2658}},
volume = {{51}},
year = {{2002}},
}