Variation in the calpain-10 gene affects blood glucose levels in the British population.

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
• Journal: Diabetes (Diabetes) Vol. 51 Issue 1 Pg. 247-50 (Jan 2002) ISSN: 0012-1797 [Print] 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)
• Female
• Genetic Variation
• Glucose Tolerance Test
• Humans
• Insulin (blood)
• Ireland (ethnology)
• Male
• Middle Aged
• Polymerase Chain Reaction
• United Kingdom
• White People