TY - JOUR
T1 - Variant in sulfonylurea receptor-1 gene is associated with high insulin concentrations in non-diabetic Mexican Americans
T2 - SUR-1 gene variant and hyperinsulinemia
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
PY - 1998/10/26
Y1 - 1998/10/26
N2 - 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.
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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U2 - 10.1007/s004390050817
DO - 10.1007/s004390050817
M3 - Article
C2 - 9799081
AN - SCOPUS:0031702660
VL - 103
SP - 280
EP - 285
JO - Human Genetics
JF - Human Genetics
SN - 0340-6717
IS - 3
ER -