Variant in sulfonylurea receptor-1 gene is associated with high insulin concentrations in non-diabetic Mexican Americans: SUR-1 gene variant and hyperinsulinemia

Hum Genet. 1998 Sep;103(3):280-5. doi: 10.1007/s004390050817.


The high-affinity sulfonylurea receptor (SUR1) gene regulates insulin secretion and may play a role in type 2 diabetes. A silent variant in exon 31 of SUR1 (AGG-->AGA) was detected by single-strand conformational polymorphism and genotypes were determined for 396 Mexican American subjects (289 non-diabetic). The normal and mutant alleles were designated G and A, respectively. Among non-diabetics, those with the AA genotype had higher fasting insulin values than those with the AG and GG genotypes (113.4 pmol/l for AA vs 82.8 pmol/l for AG/GG, P=0.043). Similar results were observed for 2-h insulin (849.6 pmol/l for AA vs 498.6 pmol/l for AG/GG, P=0.0003) and for the proinsulin to specific insulin ratio (0.068 for AA vs 0.056 for AG/GG, P=0.030). Specific insulin levels also differed significantly across the three genotypic classes (P=0.021). No differences in fasting glucose, body mass index, or waist circumference according to genotype were noted. Two-hour glucose was modestly higher in individuals with the AA genotype. Since we have previously reported linkage between SUR1 and hyperglycemia, the present association between a SUR1 variant and hyperinsulinemia in normal individuals from a high diabetes risk ethnic group raises the possibility of primary insulin hypersecretion as an antecedent of type 2 diabetes in at least some individuals from this population.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP-Binding Cassette Transporters*
  • Adult
  • Blood Glucose / analysis
  • DNA Mutational Analysis
  • Diabetes Mellitus, Type 2 / etiology
  • Female
  • Genotype
  • Humans
  • Hyperinsulinism / ethnology*
  • Insulin / blood*
  • Male
  • Membrane Proteins / genetics
  • Polymorphism, Genetic / genetics
  • Potassium Channels / genetics*
  • Potassium Channels, Inwardly Rectifying*
  • Proinsulin / blood
  • Receptors, Drug / genetics*
  • Sulfonylurea Receptors
  • United States / ethnology


  • ABCC8 protein, human
  • ATP-Binding Cassette Transporters
  • Blood Glucose
  • Insulin
  • Membrane Proteins
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Drug
  • Sulfonylurea Receptors
  • Proinsulin