title: 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.affiliation: School of Clinical Medical Sciences, the Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Lynn
authors.forename: Julie C
authors.initials: JC
authors.lastname: Evans
authors.forename: Christopher
authors.initials: C
authors.lastname: White
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Frayling
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
authors.forename: Doug M
authors.initials: DM
authors.lastname: Turnbull
authors.forename: Yukio
authors.initials: Y
authors.lastname: Horikawa
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
authors.forename: Graeme I
authors.initials: GI
authors.lastname: Bell
authors.forename: Mark
authors.initials: M
authors.lastname: Walker
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D001824:Body Constitution; D015992:Body Mass Index; D002154:Calpain / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007494:Ireland / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D006113:United Kingdom; D044465:White People
chemical_list: D001786:Blood Glucose; D007328:Insulin; D002154:Calpain; C415197:calpain 10