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

    Research output: Contribution to journalArticle

    43 Citations (Scopus)

    Abstract

    Original languageEnglish
    Pages (from-to)280-285
    Number of pages6
    JournalHuman Genetics
    Volume103
    Issue number3
    DOIs
    StatePublished - 1998

    Fingerprint

    Sulfonylurea Receptors
    Hyperinsulinism
    Insulin
    Genotype
    Genes
    Type 2 Diabetes Mellitus
    Fasting
    Glucose
    Proinsulin
    Waist Circumference
    Ethnic Groups
    Hyperglycemia
    Exons
    Body Mass Index
    Alleles
    Population

    ASJC Scopus subject areas

    • Genetics(clinical)
    • Genetics

    Cite this

    Goksel, D. L., Fischbach, K., Duggirala, R., Mitchell, B. D., Aguilar-Bryan, L., Blangero, J., ... O'Connell, P. (1998). Variant in sulfonylurea receptor-1 gene is associated with high insulin concentrations in non-diabetic Mexican Americans: SUR-1 gene variant and hyperinsulinemia. Human Genetics, 103(3), 280-285. https://doi.org/10.1007/s004390050817

    Variant in sulfonylurea receptor-1 gene is associated with high insulin concentrations in non-diabetic Mexican Americans : SUR-1 gene variant and hyperinsulinemia. / Goksel, Denise L.; Fischbach, Kathryn; Duggirala, Ravindranath; Mitchell, Braxton D.; Aguilar-Bryan, Lydia; Blangero, John; Stern, Michael P.; O'Connell, Peter.

    In: Human Genetics, Vol. 103, No. 3, 1998, p. 280-285.

    Research output: Contribution to journalArticle

    Goksel, DL, Fischbach, K, Duggirala, R, Mitchell, BD, Aguilar-Bryan, L, Blangero, J, Stern, MP & O'Connell, P 1998, 'Variant in sulfonylurea receptor-1 gene is associated with high insulin concentrations in non-diabetic Mexican Americans: SUR-1 gene variant and hyperinsulinemia', Human Genetics, vol. 103, no. 3, pp. 280-285. https://doi.org/10.1007/s004390050817
    Goksel, Denise L. ; Fischbach, Kathryn ; Duggirala, Ravindranath ; Mitchell, Braxton D. ; Aguilar-Bryan, Lydia ; Blangero, John ; Stern, Michael P. ; O'Connell, Peter. / Variant in sulfonylurea receptor-1 gene is associated with high insulin concentrations in non-diabetic Mexican Americans : SUR-1 gene variant and hyperinsulinemia. In: Human Genetics. 1998 ; Vol. 103, No. 3. pp. 280-285.
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    abstract = "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.",
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    AU - Goksel, Denise L.

    AU - Fischbach, Kathryn

    AU - Duggirala, Ravindranath

    AU - Mitchell, Braxton D.

    AU - Aguilar-Bryan, Lydia

    AU - Blangero, John

    AU - Stern, Michael P.

    AU - O'Connell, Peter

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    AB - 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.

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