Sulfonylurea receptor 1 gene variants are associated with gestational diabetes and type 2 diabetes but not with altered secretion of insulin
Sulfonylurea receptor 1 gene variants are associated with gestational diabetes and type 2 diabetes but not with altered secretion of insulin
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DOI：
10.2337/diacare.23.1.70
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发表时间：
2000-01-01
期刊：
影响因子：
16.2
通讯作者：
Laakso, M
中科院分区：
文献类型：
--
作者：
Rissanen, J;Mykkänen, L;Laakso, M
目的：研究磺脲类药物受体1（SUR 1）基因核苷酸结合折叠区变异与妊娠期糖尿病（GDM）、2型糖尿病、研究设计和方法-SUR 1基因的核苷酸结合折叠区域用聚合酶链反应扩增，并通过单克隆抗体筛选。42例妊娠期糖尿病和40例2型糖尿病患者链构象多态性分析通过限制性片段长度多态性分析，在377名血糖正常的受试者中进一步研究了检测到的变异。在295 normoglycemic subjects.RESULTS-在GDM或2型糖尿病受试者中，一个氨基酸的变化（S1369 A），四个沉默的取代（R1273 R，L 829 L，T759 T，和K649 K），和三个内含子的变异体的第一时相胰岛素分泌的影响进行了研究，在核苷酸结合折叠区的SUR 1基因。外显子16剪接受体位点的tagGCC等位基因在GDM（0.55等位基因频率，n = 42）和2型糖尿病（0.60，n = 40）受试者中的频率高于血糖正常受试者（0.43，n = 377）（分别为P-1 = 0.024和P-2 = 0.009）。同样，R1273 R多态性的AGG等位基因在GDM（0.87）和2型糖尿病（0.87）受试者中比血糖正常受试者（0.74）更常见（分别为P-1 = 0.009和P-2 = 0.001）。然而，S1369 A，R1273 R，和cagGCC-->tagGCC变异的SUR 1基因与改变第一时相胰岛素分泌在295 normoglycemic subjects.CONCLUSIONS-这些结果表明，功能变异，有助于GDM和2型糖尿病的风险可能位于接近SUR 1基因。
OBJECTIVE- To investigate the possible association of the variants in the nucleotide binding fold regions of the sulfonylurea receptor 1 (SUR1) gene with gestational diabetes mellitus (GDM), type 2 diabetes, and altered insulin secretion in Finnish subjects.RESEARCH DESIGN AND METHODS- The nucleotide binding fold regions of the SUR1 gene were amplified with polymerase chain reaction and screened by the single-strand conformational polymorphism analysis in 42 subjects with GDM and 40 subjects with type 2 diabetes. Detected variants were further investigated in 377 normoglycemic subjects by restriction fragment length polymorphism analysis. The effect of the variants of the SUR1 gene on first-phase insulin secretion was studied in 295 normoglycemic subjects.RESULTS- In subjects with GDM or type 2 diabetes, one amino acid change (S1369A), four silent substitutions (R1273R, L829L, T759T, and K649K), and three intron variants were identified in the nucleotide binding fold regions of the SUR1 gene. A tagGCC allele of exon 16 splice acceptor site was more frequent in subjects with GDM (0.55 allele frequency, n = 42) and type 2 diabetes (0.60, n = 40) than in normoglycemic subjects (0.43, n = 377) (P-1 = 0.024 and P-2 = 0.009, respectively). Similarly, an AGG allele of the R1273R polymorphism was more common in subjects with GDM (0.87) and type 2 diabetes (0.87) than in normoglycemic subjects (0.74) (P-1 = 0.009 and P-2 = 0.001, respectively). However, the S1369A, R1273R, and cagGCC-->tagGCC variants of the SUR1 gene were not associated with altered first-phase insulin secretion in 295 normoglycemic subjects.CONCLUSIONS- These results suggest that a functional variant that contributes to the risk of GDM and type 2 diabetes may locate close to the SUR1 gene.