The SPINK1 N34S mutation is not associated with Type 2 diabetes mellitus in a population of the USA

Abstract

Aims: Mutations in the serine protease inhibitor (SPINK1) gene have been associated with all forms of chronic pancreatitis. Recently, an association of SPINK1 mutations with early-onset Type 2 diabetes mellitus has been reported in patients from Bangladesh. Therefore, we determined the frequency of SPINK1 N34S mutations in patients with Type 2 diabetes mellitus from the USA. Methods: The study population of Hispanic and non-Hispanic white people consisted of 387 patients with Type 2 diabetes and familial clustering of the disease, 232 family members without diabetes, 259 patients with Type 2 diabetes without a family history, and 302 ethnically matched healthy controls as part of the San Luis Valley Diabetes Study. We performed linkage- and association-analysis in 82 multiplex families with Type 2 diabetes mellitus. Results: No significant linkage or allele sharing was detected between Type 2 diabetes mellitus and the SPINK1 locus. The frequency of the N34S mutation was determined by fluorescence polarization and was similar between patients (n = 14/387 patients with familial clustering; n = 2/259 patients without family history) and controls (n = 5/232 family members without diabetes; n = 10/302 individuals). Variables such as ethnicity, age of diabetes onset and percentage of individuals with impaired glucose tolerance did not differ significantly between carriers and homozygous normal individuals. Conclusion: The SPINK1 N34S mutation appears not to predispose Hispanic or non-Hispanic white people from the USA to the development of Type 2 diabetes mellitus. © 2005 Diabetes UK.