Non-Diabetik Metabolik Sendromda İCAM-1 E469K ve E-Selektin S128R Polimorfizmleri

Yıl 2015, Cilt: 12 Sayı: 1, 58 - 66, 15.04.2015

Halit Akbas Elif Oguz Suzan Tabur Mahmut Balkan , Hakan Korkmaz Belgin Alasehirli

Öz

Amaç: Metabolik sendrom (MetS), abdominal obezite ile ilişkili viseral yağ, insulin direnci, dislipidemi ve
hipertansiyon gibi sistemik bozuklukların bir grubudur. İnflamasyon biyomarkırları ile endotelyal
disfonksiyon, metabolik sendrom ve inflamatuar şartlarla ilişkilendirilmiştir. Son çalışmalar inflamatuar
genlerdeki genetik varyasyonların metabolik sendromda kilit rol oynadığını ileri sürmektedirler. Bu
çalışmada non-diabetik MetS li hastalarda, inflamatuar genlerden İCAM-1 ve E-selektin gen
polimorfizmlerinin araştırılması amaçlanmıştır.
Metod: Çalışmaya non-diabetik MetS'li 132 hasta ve 118 kontrol örneği dahil edilmiştir. İCAM-1 E469K
(1462A>G ;rs5498) ve E-selektin S128R (561A>C;rs5361) gen polimorfizmlerini belirlemek için polimeraz
zincir reaksiyonu- restriksiyon parça uzunluk polimorfizmi (PCR-RFLP) tekniği uygulanmıştır.

Bulgular: Kontrol grubuna kıyasla, non-diabetik MetS'li hastalarda Hem İCAM-1 E469K hemde E selektin
S128R polimorfizmlerinin genotip dağılımı ve allel frekanslarında herhangi bir değişiklik saptanmamıştır.
Sonuç: Bu çalışma, non-diabetik MetS'lu hastalarda İCAM-1 E469K ve E selektin S128R
polimorfizmlerinin araştırıldığı ilk çalışmadır. Bu çalışmadan elde edilen veriler, İCAM-1 E469K ve E
selektin S128R gen polimorfizmlerinin Türk populasyonundaki non-diabetik MetS ile ilişkili olmadığını
göstermiştir.

Anahtar Kelimeler

Metabolik sendrom, İCAM-1, E-Selektin, gen polimorfizmi, Polimeraz zincir reaksiyonu

ICAM-1 E469K and E-Selectin S128R Polymorphisms with Non-Diabetic Metabolic Syndrome

Öz

Backgrounds: Metabolic syndrome (MetS) is a cluster of abdominal obesity linked to an excess of visceral
fat, insülin resistance, dyslipidemia and hypertension. Inflammation biomarkers and endothelial dysfunction
is associated with metabolic syndrome (MetS) and inflammatory condition. Recent studies suggest that
genetic variation in inflammatory genes plays a pivotal role in MetS. We aimed to investigate the
polymorphisms of two inflammatory genes, ICAM-1 and E-selectin with non-diabetic MetS in Turkish
population.
Methods: The study included 132 patients with non-diabetic MetS. and 118 control subjects. Polymerase
chain reaction-restriction fragment length polymorphism (PCR-RFLP) method were used to determine the E
selectin S128R (561A>C;rs5361) and ICAM-1 E469K (1462A>G;rs5498) polymorphisms.
Results: There was no change in genotype and allele frequencies in both ICAM-1 E469K and E selectin
S128R polymorphisms compared to control subjects.
Conclusions: The realtionship between ICAM-1 and E-selectin polymorphisms and non-diabetic MetS was
investigated firstly examined in this study. The data of this study suggest that ICAM-1 E469K and E-selectın
S128R polymorphisms are not in susceptibility to non-diabetic MetS in the Turkish population

Anahtar Kelimeler

Metabolic syndrome, ICAM-1, E-Selectin, gene polymorphism, Polymerase Chain Reaction

Kaynakça

• 1.De Luca C, Olefsky JM. Inflammation and insulin resistance. FEBS Lett 2008; 582 (1):97-105. 2.Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr; Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009;120 (16):1640-5. 3.Scholze J, Alegria E, Ferri C, Langham S, Stevens W, Jeffries D, Uhl-Hochgraeber K. Epidemiological and economic burdenof metabolic syndrome and its consequences in patients with hypertension in Germany, Spain and Italy; a prevalence-based model. BMC Public Health 2010; 2 (10): 529. 4.Shen J, Goyal A, Sperling L. The emerging epidemic of obesity, diabetes, and the metabolic syndrome in china. Cardiol Res Pract 2012;2012: 178675. 5.Grundy SM. Metabolic syndrome pandemic. ArteriosclerThromb Vasc Biol 2008; 28 (4):629-636. MensahGA 6.1, Mokdad AH, Ford E, Narayan KM, Giles WH, Vinicor F, Deedwania PCObesity, metabolic syndrome, and type 2 diabetes: emerging epidemics and their cardiovascular implications. Cardiol Clin 2004;22 (4):485-504. 7.Dandona P, Aljada A, Chaudhuri A, Mohanty P, Garg R. Metabolic syndrome: a comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation 2005;111 (11):1448-54. Tuttolomondo A 8.1, Pecoraro R, Di Raimondo D, Di Sciacca R, Canino B, Arnao V, Buttà C, Della Corte V, Maida C, Licata G, Pinto A.Immune-inflammatory markers and arterial stiffness indexes in subjects with acute ischemic stroke with and without metabolicsyndrome. Diabetol Metab Synd. 2014;6 (1):28. 9.Rubin D, Claas S, Pfeuffer M, Nothnagel M, Foelsch UR, Schrezenmeir J. s-ICAM-1 and s-VCAM-1 in healthy men are strongly associated with traits of themetabolicsyndrome, becoming evident in the postprandial response to a lipid-rich meal.Lipids Health Dis 2008 1;7:32. 10.McQueen MB, Bertram L, Rimm EB, Blacker D, Santangelo SL. A QTL genome scan of themetabolicsyndromeand its component traits. BMC Genet 2003;4 (1):S96. 11.Fall T, Ingelsson E. Genome-wide association studies of obesity and metabolic syndrome. Mol Cell Endocrinol 2014;382 (1):740-57. Stančáková A 12.Laakso M. Genetics of metabolic syndrome. Rev Endocr Metab Disord. 2014 Aug 16. [Epub ahead of print] 13.Hsu LA, Chang CJ, Wu S, Teng MS, Chou HH, Chang HH, Chang PY, Ko YL. Association between functional v a ri a n ts o f t h e IC AM1 a n d CRP g e n e s andmetabolicsyndromein Taiwanese subjects. Metabolism 2010;59 (12):1710-6. Gomez-DelgadoF 14.Alcala-Diaz JF, Garcia-Rios A, Delgado-Lista J, Ortiz-Morales A, Rangel-Zuñiga O, Tinahones FJ, Gonzalez-Guardia L, Malagon MM, Bellido-Muñoz E, Ordovas JM, Perez-Jimenez F, Lopez-Miranda J, PerezMartinez P. Polymorphism at the TNF-alpha gene interacts with Mediterranean diet to influence triglyceride metabolism and inflammation status in metabolic syndrome patients: From the CORDIOPREV clinical trial. Mol Nutr Food Res 2014;58 (7):1519-27. 15.Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA2001;285 (19):2486-97. 16.Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C; American Heart Association; National Heart, Lung, and Blood Institute. Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Circulation 2004;109 (3):433–8. 17.Akbas H., Uyanikoglu A., Aydogan T., Atay A.E., Dilmec F., Cerrah S., Akkafa F., Nar H., "E-cadherin (CDH1) gene -160C>A promoter polymorphism and Risk of Gastric and Esophageal Cancers", Acta Medica Mediterranea 2013 29; 671-676. 18.Shaker O, Zahra A, Sayed A, Refaat A, El-Khaiat Z, Hegazy G, El-Hindawi K, Ay-El Deen M. Role of ICAM-1 and E-selectin gene polymorphisms in pathogenesis of PAOD in Egyptian patients. Vasc Health Risk Manag 2010; 4 (6):9-15. Tripathi R 19.Singh PK, Tewari S, Tamhankar PM, Ramesh V, Agarwal S. Genetic predisposition of E-selectin gene (S128R) polymorphism in patients with coronary artery disease (CAD). Indian J MedRes 2009130 (4):423-7. Roy S 20.Das S, Danaboina R, Sharma V, Kaul S, Jyothy A, Munshi A. Association of E-selectin gene polymorphism (S128R) with ischemic stroke and stroke subtypes. Inflammation 2014;37 (2):599-603. 21.Ma J, Zhang D, Brismar K, Efendic S, Gu HF. Evaluation of the association between the common E469K polymorphism in the ICAM-1 gene and diabetic nephropathy among type 1 diabetic patients in GoKinD population. BMC Med Genet 2008;27 (9): 47. 22.Millern J, Knorr R, Ferrone M, Houdei R, Carron CP, Dustin ML.Intercellular adhesion molecule-1 dimerization and its consequences for adhesion mediated by lymphocytefunction associated-1.J Exp Med. 1995;182 (5):1231-41. 23.Vallejo R, Fidalgo-Perez I, Malo C, Paredes MM, Kramer J, Spinal neuromodulation: a novel approach in the management of peripheral vascular disease. Tech Reg Anesth Pain Mana 2006,10 (1):3–6 Liu ZP 24.Huo Y, Li JP, Zhang Y, Xue L, Zhao CY, Hong XM, Huang AQ, Gao W. Polymorphism K469E of intercellular a d h e s i o n m o l e c u l e - 1 g e n e a n d restenosisaftercoronarystenting in Chinesepatients. Chin Med J (Engl). 2004;117 (2):172-5 Liu LZ 25.Wu EP, Liu HL. Relation between K469E gene polymorphism of ICAM-1 and recurrence of ACS and cardiovascular mortality.Asian Pac J Trop Med 2013;6 (11):916-20. Lu CH 26. Hwang CW, Chen NF, Liu WS, Wu WT.Association of intercellular adhesion molecular-1 gene polymorphism in ischemic stroke patients.Ann Indian Acad Neurol 2013 ;16 (3):380-3. Barresi V 27. Signorelli SS, Musso N, Anzaldi M, Fiore V, Alberghina M. ICAM-1 and SRD5A1 gene polymorphisms in symptomatic peripheral artery disease. Vasc Med 2014;19 (3):175-181. 28. Rao RM, Haskard DO, Landis RC. Enhanced recruitment of Th2 and CLA-negative lymphocytes by the S128R polymorphism of E-selectin. Journal of Immunology 2002;169 (10): 860–5865. Alessandro R 29. Seidita G, Flugy AM, Damiani F, Russo A, Corrado C, Colomba P, Gullotti L, Buettner R, Bruno L, De Leo G. Role of S128R polymorphism of E-selectin in colon metastasis formation. Int J Cancer 2007;121 (3):528-35. Wang Z 30. Xu Y, Chen S, Wang L, Ding H, Lu G, Wang D, Zhai Z, Duan J, Zhang W.A common missense single nucleotide polymorphism in the E-selectin gene is significantly associated with essential hypertension in the Han population but only weakly associated in the Uygur population. Hypertens Res 2012;35 (4):413-7. 31. Chen HL, Hua Q, Liu RK, Yang Z. Effect ofEselectinA561C (S128R) polymorphism on blood pressure. Zhonghua Xin Xue Guan Bing Za Zhi 2005;33 (7):603-7. 32. Klöting N, B lüher M Adipocyte dysfunction, inflammation and metabolic syndrome. Rev Endocr Metab Disord. 2014 Oct 26. [Epub ahead of print] 33. Milagro F, Campión J, Martínez JA.Weight gain induced by high-fat feeding involves increased liver oxidative stress. Obesity (Silver Spring) 2006 ;14 (7):1118-23. 34. Fujita K, Nishizawa H, Funahashi T, Shimomura I, Shimabukuro M. Systemicoxidativestress is associated w i t h v i s c e r a l f a t a c c u m u l a t i o n a n d themetabolicsyndrome.Circ J 2006 ;70 (11):1437-42. 35. Chung SW, Kang SG, Rho JS, Kim HN, Song IS, Lee YA, Heo SJ, Song SW. The Association betweenOxidativeStress andMetabolicSyndrome in Adults.Korean J Fam Med 2013;34 (6):420-8. Bassols J 36. Ortega FJ, Moreno-Navarrete JM, Peral B, Ricart W, Fernández-Real JM. Study of the proinflammatory role of human differentiated omental adipocytes. J Cell Biochem 2009 ;107 (6):1107-17. Meijer K 37. de Vries M, Al-Lahham S, Bruinenberg M, Weening D, Dijkstra M, Kloosterhuis N, van der Leij RJ, van der Want H, Kroesen BJ, Vonk R, Rezaee F. Human primary adipocytes exhibit immune cell function: adipocytes prime inflammation independent of macrophages. PLoS One 2011;6 (3):e17154.