Rissanen J, Markkanen A, Kärkkäinen P, Pihlajamäki J, Kekäläinen P, Mykkänen L, Kuusisto J, Karhapää P, Niskanen L, Laakso M
Department of Medicine, University of Kuopio, Finland.
Diabetes Care. 2000 Jan;23(1):70-3. doi: 10.2337/diacare.23.1.70.
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.
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.
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) (P1 = 0.024 and P2 = 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) (P1 = 0.009 and P2 = 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.
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.
研究芬兰人群中磺脲类受体1（SUR1）基因核苷酸结合折叠区变异与妊娠期糖尿病（GDM）、2型糖尿病及胰岛素分泌改变之间的可能关联。
采用聚合酶链反应扩增SUR1基因的核苷酸结合折叠区，并对42例GDM患者和40例2型糖尿病患者进行单链构象多态性分析筛选。通过限制性片段长度多态性分析在377例血糖正常的受试者中进一步研究检测到的变异。在295例血糖正常的受试者中研究SUR1基因变异对第一相胰岛素分泌的影响。
在GDM或2型糖尿病患者中，SUR1基因核苷酸结合折叠区鉴定出1个氨基酸改变（S1369A）、4个沉默替换（R1273R、L829L、T759T和K649K）以及3个内含子变异。外显子16剪接受体位点的tagGCC等位基因在GDM患者（等位基因频率0.55，n = 42）和2型糖尿病患者（0.60，n = 40）中比血糖正常的受试者（0.43，n = 377）更常见（P1 = 0.024，P2 = 0.009）。同样，R1273R多态性的AGG等位基因在GDM患者（0.87）和2型糖尿病患者（0.87）中比血糖正常的受试者（0.74）更常见（P1 = 0.009，P2 = 0.001）。然而，SUR1基因的S1369A、R1273R和cagGCC→tagGCC变异与295例血糖正常受试者的第一相胰岛素分泌改变无关。
这些结果表明，可能存在一个导致GDM和2型糖尿病风险增加的功能性变异，其可能位于SUR1基因附近。
