title: The SPINK1 N34S mutation is not associated with Type 2 diabetes mellitus in a population of the USA.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Schneider
authors.forename: E C
authors.initials: EC
authors.lastname: Lawrence
authors.forename: M M
authors.initials: MM
authors.lastname: Barmada
authors.forename: J M
authors.initials: JM
authors.lastname: Norris
authors.forename: R F
authors.initials: RF
authors.lastname: Hamman
authors.forename: J A
authors.initials: JA
authors.lastname: Marshall
authors.forename: R E
authors.initials: RE
authors.lastname: Ferrell
authors.forename: D C
authors.initials: DC
authors.lastname: Whitcomb
mesh_terms: D002908:Chronic Disease; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000235:genetics; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000235:genetics*
chemical_list: D014359:Trypsin Inhibitor, Kazal Pancreatic