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

Denise L. Goksel, Kathryn Fischbach, Ravindranath Duggirala, Braxton D. Mitchell, Lydia Aguilar-Bryan, John Blangero, Michael P. Stern, Peter O'Connell

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    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.

    Original languageEnglish (US)
    Pages (from-to)280-285
    Number of pages6
    JournalHuman Genetics
    Issue number3
    StatePublished - Oct 26 1998


    ASJC Scopus subject areas

    • Genetics
    • Genetics(clinical)

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