Erkan SÖĞÜT, Osman EVLİYAOĞLU, Nuriye UZUNCAN, Mustafa Kemal BAŞARILI, Enver SANCAKTAR, Baysal KARACA

Association of a single nucleotide polymorphism in the SUR1 gene with type 2 diabetes and obesity in Turkish patients

Amaç: Sulfonylurea receptor 1 (SUR1) geni SUR1 proteinini kodlayarak glukozla indüklenen insülin sekresyonunda anahtar rolü oynar. Bu çalışmanın amacı, SUR1 geninin 31. ekzonundaki polimorfizm ile Tip 2 diyabet arasındaki ilişkiyi ve diyabetik hastalardaki obezite ile beraberliğini araştırmaktır. Gereç ve yöntem: Diyabet polikliniğinde takip edilen 90 hasta (45 kadın, 45 erkek ) çalışmaya dahil edildi. Serumda glukoz, trigliserid, kolesterol ve tam kanda HbA1c değerleri belirlendi. 31. Egzondaki SNP’ler ise polymeraz zincir reaksiyon / restriksiyon fragment uzunluk polymorphism (PCR-RFLP) yöntemiyle belirlendi. Bulgular: Kontrol grubu ile karşılaştırıldığında Tip 2 diyabetik hastalarda A allel frekansının artmış olduğu gözlendi (%41 ve %24, p

Türk toplumunda tip 2 diyabetin ve obezitenin, SUR1 genindeki tek nükleotit polimorfizmi ile birlikteliği

Objectives: Sulfonylurea receptor 1 (SUR1) gene codes the SUR1 protein that plays a key role in glucose-induced insulin secretion. In this study, we have investigated the relationship between the polymorphism in exon 31 of the SUR1 gene and type 2 diabetes, and its association with obesity in Turkish diabetic patients. Materials and methods: 90 patients (45 males and 45 females, aged 43-70 years old) who were followed up in the diabetes outpatient clinic were enrolled in the study. Serum glucose, triglyceride, cholesterol and blood HbA1c levels were determined. The SNPs in exon 31 were examined by a polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) method. Results: A significant increase in the frequency of the A allele was observed in type 2 diabetic patients compared with that of the control group (41% vs. 24%, p

PDF

___

1. American Diabetes Association. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1997; 20(7): 1183-97.
2. Ashcroft FM, Gribble FM. ATP-sensitive K+ channels and insulin secretion: their role in health and disease. Diabetologia 1999; 42(8): 903-19.
3. Inagaki N, Gonoi T, Clement JP, et al. Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor. Science 1995; 270(5239): 1166-70.
4. Aguilar-Bryan L, Bryan J. Molecular biology of adenosine triphosphate-sensitive potassium channels. Endocrine Rev 1999; 20(2): 101-35.
5. Thomas PM, Wohllk N, Huang E, et al. Inactivation of the first nucleotide-binding fold of the sulfonylurea receptor, and familial persistent hyperinsulinemic hypoglycemia of infancy. Am J Hum Genet 1996; 59(3): 510-18.
6. DeFronzo RA. Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes. Diabetes Reviews 1997; 5(3): 177-85.
7. Velho G, Froguel P. Genetic determinants of non-insulindependent diabetes mellitus: strategies and recent results. Diabetes Metab 1997; 23(1): 7-17.
8. Hani EH, Clément K, Velho G, et al. Genetic studies of the sulfonylurea receptor gene locus in NIDDM and in morbid obesity among French Caucasians. Diabetes 1997; 46(4): 688-94.
9. Hansen T, Echwald SM, Hansen L, et al. Decreased tolbutamide- stimulated insulin secretion in healthy subjects with sequence variants in the high-affinity sulfonylurea receptor gene. Diabetes 1998; 47(4): 598-605.
10. Hart LM, de Knijff P, Dekker JM, et al. Variants in the sulphonylurea receptor gene: association of the exon 16-3t variant with Type II diabetes mellitus in Dutch Caucasians. Diabetologia 1999; 42(5): 617-20.
11. Goksel DL, Fischbach K, Duggirala R, et al. Variant in sulfonylurea receptor-1 gene is associated with high insulin concentrations in non-diabetic Mexican Americans: SUR-1 gene variant and hyperinsulinemia. Hum Genet 1998; 103(3): 280-5.
12. Reis AF, Ye WZ, Dubois-Laforgue D, Bellanne-Chantelot C, Timsit J, Velho G. Association of a variant in exon 31 of the sulfonylurea receptor 1 (SUR1) gene with type 2 diabetes mellitus in French Caucasians. Hum Genet 2000; 107(2): 138-44.
13. Thomas PM, Cote GJ, Hallman DM, Mathew PM. Homozygosity mapping, to chromosome 11p, of the gene for familial persistent hyperinsulinemic hypoglycemia of infancy. Am J Hum Genet 1995; 56(2): 416-21.
14. Hamming KS, Soliman D, Matemisz LC, et al. Coexpression of the type 2 diabetes susceptibility gene variants KCNJ11 E23K and ABCC8 S1369A alter the ATP and sulfonylurea sensitivities of the ATP-sensitive K(+) channel. Diabetes 2009;58(10):2419-24.
15. Elbein SC, Sun J, Scroggin E, Teng K, Hasstedt SJ. Role of common sequence variants in insulin secretion in familial type 2 diabetic kindreds: the sulfonylurea receptor, glucokinase, and hepatocyte nuclear factor 1alpha genes. Diabetes Care 2001; 24(3): 472-8.
16. Hart LM, Dekker JM, Van Haeften TW, et al. Reduced second phase insulin secretion in carriers of a sulphonylurea receptor gene variant associating with Type II diabetes mellitus. Diabetologia 2000; 43(4): 515-9.
17. Weisnagel SJ, Rankinen T, Nadeau A, et al. Decreased fasting and oral glucose stimulated C-peptide in nondiabetic subjects with sequence variants in the sulfonylurea receptor 1 gene. Diabetes 2001; 50(3): 697-702.
18. Inoue H, Ferrer J, Welling CM, et al. Sequence variants in the sulfonylurea receptor (SUR) gene are associated with NIDDM in Caucasians. Diabetes 1996; 45(6): 825-31.
19. Rissanen, J, Markkanen A, Karkkainen P, et al. Sulfonylurea receptor 1 gene variants are associated with gestational diabetes and type 2 diabetes but not with altered secretion of insulin. Diabetes Care 2000; 23(1): 70-3.
20. Ohta, Y, Tanizawa Y, Inoue H, et al. Identification and functional analysis of sulfonylurea receptor 1 variants in Japanese patients with NIDDM. Diabetes 1998; 47(3): 476-81.
21. Yki-Järvinen H. Pathogenesis of non-insulin dependent diabetes mellitus. Lancet 1994; 343(8889): 91-5.
22. Dworacka M, Winiarska H, Jagodziński PP. Impact of the sulfonylurea receptor 1 (SUR1) exon 16-3c/t polymorphism on acute hyperglycaemia in type 2 diabetic patients. Diabetes Res Clin Pract 2007;77(2):258-62.
23. O’Rahilly S, Gray H, Humphreys PJ, et al. Impaired processing of prohormones associated with abnormalities of glucose homeostasis and adrenal function. N Engl J Med 1995; 333(9): 1386-90
24. Yokoi N, Kanamori M, Horikawa Y, et al.Association studies of variants in the genes involved in pancreatic beta-cell function in type 2 diabetes in Japanese subjects. Diabetes 2006 ;55(8):2379-86.
25. Jones JM, Meisler MH, Seldin MF, Lee BK, Eicher EM. Localization of insulin-2 (Ins-2) and the obesity mutant tubby (tub) to distinct regions of mouse chromosome 7. Genomics 1992; 14(1): 197-9.
26. van Tilburg JH, Sandkuijl LA, Franke L, et al. Genomewide screen in obese pedigrees with type 2 diabetes mellitus from a defined Dutch population. Eur J Clin Invest 2003; 33(12): 1070-4.
27. Tarasov AI, Nicolson TJ, Riveline JP, et al. A rare mutation in ABCC8/SUR1 leading to altered ATP-sensitive K+ channel activity and beta-cell glucose sensing is associated with type 2 diabetes in adults. Diabetes 2008;57(6):1595-604.
28. Shi H, Moustaid-Moussa N, Wilkison WO, Zemel MB. Role of the sulfonylurea receptor in regulating human adipocyte metabolism. FASEB J 1999; 13(13): 1833-8.
29. Gabrielsson BG, Karlsson AC, Lonn E, et al. Molecular characterization of a local sulfonylurea system in human adipose tissue. Mol Cell Biochem 2004; 258(1-2): 65-71.