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

被引:45
作者
Goksel, DL
Fischbach, K
Duggirala, R
Mitchell, BD
Aguilar-Bryan, L
Blangero, J
Stern, MP
O'Connell, P
机构
[1] Univ Texas, Hlth Sci Ctr, Dept Med, Div Clin Epidemiol, San Antonio, TX 78284 USA
[2] Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA
[3] Univ Oxford, Inst Biol Anthropol, Oxford, England
[4] SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA
[5] Baylor Coll Med, Dept Med, Houston, TX 77030 USA
关键词
D O I
10.1007/s004390050817
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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 (AG (G) under bar-->AG (A) under bar) 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 raiser 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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页码:280 / 285
页数:6
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