| Abstract | Variation in the calpain-10 gene (CAPN10) has been shown to be associated with type 2 diabetes in Mexican-Americans and in at least three Northern European populations. Studies in nondiabetic Pima Indians showed that one of the at-risk DNA polymorphisms, single-nucleotide polymorphism (SNP)-43, in CAPN10 was associated with insulin resistance, and individuals with the G/G-genotype had significantly higher fasting plasma glucose and 2-h insulin concentrations after a 75-g oral glucose tolerance test (OGTT). We have examined the effect of variation in CAPN10 on plasma glucose and insulin levels in a group of 285 nondiabetic British subjects after a 75-g OGTT. The results showed that subjects with G/G genotype at SNP-43 had higher 2-h plasma glucose levels than the combined G/A + A/A group (P = 0.05). We also examined the SNP-43, -19, and -63 haplotype combination 112/121, which is associated with an approximately threefold increased risk of diabetes. Subjects with the 112/121 haplotype combination (n = 29) had increased fasting (P = 0.004) and 2-h plasma glucose levels (P = 0.003) compared with the rest of the study population after correction for age, sex, and BMI. The 112/121 haplotype combination was also associated with a marked decrease in the insulin secretory response, adjusted for the level of insulin resistance (P = 0.002). We conclude that genetic variation in the CAPN10 gene influences blood glucose levels in nondiabetic British subjects and that this is due, at least in part, to the effects of calpain-10 on the early insulin secretory response. |
| Authors | Stephen Lynn, Julie C Evans, Christopher White, Timothy M Frayling, Andrew T Hattersley, Doug M Turnbull, Yukio Horikawa, Nancy J Cox, Graeme I Bell, Mark Walker
(Affiliation: School of Clinical Medical Sciences, the Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, UK.)
|
| Journal | Diabetes
(Diabetes)
Vol. 51
Issue 1
Pg. 247-50
(Jan 2002)
ISSN: 0012-1797 United States |
| PMID | 11756349
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
| Chemical References |
- Blood Glucose
- Insulin
- Calpain
- calpain 10
|
| Topics |
- Adult
- Aged
- Blood Glucose
(metabolism)
- Body Constitution
- Body Mass Index
- Calpain
(genetics)
- European Continental Ancestry Group
- Female
- Genetic Variation
- Glucose Tolerance Test
- Great Britain
- Humans
- Insulin
(blood)
- Ireland
(ethnology)
- Male
- Middle Aged
- Polymerase Chain Reaction
|
