Variant in sulfonylurea receptor-1 gene is associated with high insulin concentrations in non-diabetic Mexican Americans: SUR-1 gene variant and hyperinsulinemia.
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.
Goksel
D L
DL
Department of Pathology, University of Texas Health Science Center at San Antonio, USA.
Fischbach
K
K
Duggirala
R
R
Mitchell
B D
BD
Aguilar-Bryan
L
L
Blangero
J
J
Stern
M P
MP
O'Connell
P
P
D018528:ATP-Binding Cassette Transporters; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology; D005260:Female; D005838:Genotype; D006801:Humans; D006946:Hyperinsulinism / Q000208:ethnology*; D007328:Insulin / Q000097:blood*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D015221:Potassium Channels / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying; D011384:Proinsulin / Q000097:blood; D011955:Receptors, Drug / Q000235:genetics*; D064233:Sulfonylurea Receptors; D014481:United States / Q000208:ethnology
C577507:ABCC8 protein, human; D018528:ATP-Binding Cassette Transporters; D001786:Blood Glucose; D007328:Insulin; D008565:Membrane Proteins; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D011384:Proinsulin