title: Amylin gene promoter mutations predispose to Type 2 diabetes in New Zealand Maori.
abstract: OBJECTIVE
  Amylin gene mutations are known to predispose Chinese and Japanese subjects, but not Caucasian subjects, to Type 2 diabetes. New Zealand Maori, who have a high prevalence of Type 2 diabetes, have genetic origins in South East Asia. Amylin gene mutations could therefore predispose New Zealand Maori to Type 2 diabetes.
  
  
  METHODS
  The amylin gene was screened for mutations in the proximal promoter region, exons 1 and 2, intron 1, and coding region of exon 3 by polymerase chain reaction amplification and direct sequencing of 131 Type 2 diabetic Maori patients and 258 non-diabetic Maori control subjects.
  
  
  RESULTS
  We identified three new amylin gene mutations: two mutations in the promoter region (-215T>G and -132G>A) and a missense mutation in exon 3 (Q10R). The -215T>G mutation was observed in 5.4% of Type 2 Maori diabetic patients and predisposed the carrier to diabetes with a relative risk of 7.23. The -215T>G mutation was inherited with a previously described amylin promoter polymorphism (-230A>C) in 3% of the Maori with Type 2 diabetes, which suggests linkage disequilibrium exists between these two mutations. The -230A>C polymorphism on its own, however, was not associated with Type 2 diabetes in Maori subjects. The -132G>A and Q10R mutations were both observed in 0.76% of Type 2 diabetic patients and were absent in non-diabetic subjects.
  
  
  CONCLUSIONS
  The amylin gene mutations identified in this study are associated with Type 2 diabetes in 7% of Maori. Amylin is likely to be an important susceptibility gene for Type 2 diabetes in Maori people.
authors.affiliation: The Biochemistry and Molecular Biology Group, School of Biological Sciences, University of Auckland, New Zealand. nicola.poa@chmeds.ac.nz
authors.forename: N R
authors.initials: NR
authors.lastname: Poa
authors.forename: G J S
authors.initials: GJ
authors.lastname: Cooper
authors.forename: P F
authors.initials: PF
authors.lastname: Edgar
mesh_terms: D000682:Amyloid / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology* / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D058228:Islet Amyloid Polypeptide; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009520:New Zealand / Q000208:ethnology; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: D000682:Amyloid; D058228:Islet Amyloid Polypeptide