Insertion/Deletion Polymorphisms and Serum Angiotensin-converting Enzyme Levels in Iranian Patients with Sarcoidosis
Abstract
Background: Sarcoidosis is a multisystem inflammatory disease of unknown origin with characterization of small granulomas. Angiotensin-converting enzyme (ACE) is a pathophysiologic marker of sarcoidosis. We present the ACE insertion/deletion (I/D) polymorphism in correlation with serum ACE level in Iranian patients with sarcoidosis.
Methods: From Jan 2014 to Jan 2015, 102 Iranian patients who histopathologically diagnosed for sarcoidosis and 192 healthy age and sex-matched controls were recruited. PCR was used for detection of I/D polymorphism in ACE gene.
Results: Frequency of II/ID/DD genotype in sarcoidosis disease was 17%, 35.5%, and 47.1%, respectively. The frequency of D allele was 0.65. A significant association between I/D genotypes and mean of sACE level was seen (DD=85.2±22.9, P<0.001). More frequent genotype in sarcoidosis patients was DD (47%), ID genotype (45.9%) was found more in controls. Logistic regression analysis adjusting age and sex showed that ID to II (OR=0.35, 95%CI=0.17-0.73, P=0.005) and DD to II (OR=2.11, 95%CI=0.98-4.54, P=0.05) could be considered as a predictor factor for the disease activity. No significant model for men in sarcoidosis group was seen, while women with II/ID were associated with a reduced risk for the disease.
Conclusion: Although more regional studies with appropriate statistical scale must be done to provide a better diagnosis and prognostic tool for this disease, this study demonstrates that ID and DD genotype could be predictive factors for sarcoidosis.
James DG, Sharma OP (2002). From Hutchinson to now: a historical glimpse. Curr Opin Pulm Med, 8:416-423.
Gungor S, Ozseker F, Yalcinsoy M, Akkaya E, Can G, Eroglu H, Genc NS (2015). Conventional markers in determination of activity of sarcoidosis. Int Immunopharmacol, 25:174-179.
Crommelin HA, Vorselaars AD, van Moorsel CH, Korenromp IH, Deneer VH, Grutters JC (2014). Anti-TNF therapeutics for the treatment of sarcoidosis. Immunotherapy, 6:1127-1143.
Smith G, Brownell I, Sanchez M, Prystowsky S (2008). Advances in the genetics of sarcoidosis. Clin Genet, 73:401-412.
Sarcoidosis So (1999). Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med, 160:736-755.
Newman LS, Rose CS, Bresnitz EA, Rossman MD, Barnard J, Frederick M, Terrin ML, Weinberger SE, Moller DR, McLennan G (2004). A case control etiologic study of sarcoidosis: environmental and occupational risk factors. Am J Respir Crit Care Med, 170:1324-1330.
Song Z, Marzilli L, Greenlee BM, Chen ES, Silver RF, Askin FB, Teirstein AS, Zhang Y, Cotter RJ, Moller DR (2005). Mycobacterial catalase–peroxidase is a tissue antigen and target of the adaptive immune response in systemic sarcoidosis. J Exp Med, 201:755-767.
Dubaniewicz A, Dubaniewicz-Wybieralska M, Sternau A, Zwolska Z, Iżycka-Świeszewska E, Augustynowicz-Kopeć E, Skokowski J, Singh M, Zimnoch L (2006). Mycobacterium tuberculosis complex and mycobacterial heat shock proteins in lymph node tissue from patients with pulmonary sarcoidosis. J Clin Microbiol, 44:3448-3451.
Iannuzzi MC, Maliarik MJ, Poisson LM, Rybicki BA (2003). Sarcoidosis susceptibility and resistance HLA-DQB1 alleles in African Americans. Am J Respir Crit Care Med, 167:1225-1231.
Sato H, Grutters JC, Pantelidis P, Mizzon AN, Ahmad T, van Houte A-J, Lammers J-WJ, van den Bosch JM, Welsh KI, du Bois RM (2002). HLA-DQB1* 0201: a marker for good prognosis in British and Dutch patients with sarcoidosis. Am J Respir Cell Mol Biol, 27:406-412.
van den Berg-Loonen EM, Voorter CE, Drent M (2004). Strong association of severe pulmonary sarcoidosis with HLA DQB1* 0602. Hum Im-munol, 65:S34.
Grunewald J, Brynedal B, Darlington P, Nisell M, Cederlund K, Hillert J, Eklund A (2010). Different HLA-DRB1 allele distributions in distinct clinical subgroups of sarcoidosis patients. Respir Res, 11:25.
Society AT (1999). Statement on sarcoidosis. Am J Respir Crit Care Med, 160:736-755.
Furuya K, Yamaguchi E, Itoh A, Hizawa N, Ohnuma N, Kojima J, Kodama N, Kawakami Y (1996). Deletion polymorphism in the angiotensin I converting enzyme (ACE) gene as a genetic risk factor for sarcoidosis. Thorax, 51:777-780.
Kruit A, Ruven H, Grutters J (2010). Angiotensin II receptor type 1 1166 A/C and angiotensin converting enzyme I/D gene polymorphisms in a Dutch sarcoidosis cohort. Sarcoidosis Vasc Diffuse Lung Dis, 27:147-152.
Biller H, Ruprecht B, Gaede K (2009). Gene polymorphisms of ACE and the angiotensin receptor AT2R1 influence serum ACE levels in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis, 26:139-146.
Arbustini E, Grasso M, Leo G, Tinelli C, Fasani R, Diegoli M, Banchieri N, Cipriani A, Gorrini M, Semenzato G (1996). Polymorphism of angiotensin-converting enzyme gene in sarcoidosis. Am J Respir Crit Care Med, 153:851-854.
Tomita H, Ina Y, Sugiura Y, Sato S, Kawaguchi H, Morishita M, Yamamoto M, Ueda R (1997). Polymorphism in the angiotensin-converting enzyme (ACE) gene and sarcoidosis. Am J Respir Crit Care Med, 156:255-259.
Rybicki B, Maliarik M, Poisson L, Iannuzzi M (2004). Sarcoidosis and granuloma genes: a family-based study in African-Americans. Eur Respir J, 24:251-257.
McGRATH DS, Foley PJ, Petrek M, Izakovicova-Holla L, Dolek V, Veeraraghavan S, Lympany PA, Pantelidis P, Vasku A, Wells AU (2001). Ace gene I/D polymorphism and sarcoidosis pulmonary disease severity. Am J Respir Crit Care Med,164:197-201.
Pietinalho A, Furuya K, Yamaguchi E, Kawakami Y, Selroos O (1999). The angiotensin‐converting enzyme DD gene is associated with poor prognosis in Finnish sarcoidosis patients. Eur Respir J, 13:723-726.
Mihailovic-Vucinic V, Sharma OP (2006). Atlas of Sarcoidosis: Pathogenesis, Diagnosis and Clinical Features. ed. Springer Science & Business Media.
Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA (1988). Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science, 239:487-491.
Rigat B, Hubert C, Corvol P, Soubrier F (1992). PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1)(dipeptidyl carboxypeptidase 1). Nucleic Acids Res, 20:1433.
Alia P, Mana J, Capdevila O, Alvarez A, Navarro M (2005). Association between ACE gene I/D polymorphism and clinical presentation and prognosis of sarcoidosis. Scand J Clin Lab Invest, 65:691-697.
Maliarik MJ, Rybicki BA, Malvitz E, Sheffer RG, Major M, Popovich Jr J, Iannuzzi MC (1998). Angiotensin-converting enzyme gene polymorphism and risk of sarcoidosis. Am J Respir Crit Care Med, 158:1566-1570.
Yilmaz D, Karkucak M, Coskun F (2012). ACE gene I/D polymorphism and risk of sarcoidosis development in Turkish patients. Tuberk Toraks, 60:201-206.
Schürmann M, Reichel P, Müller‐Myhsok B, Dieringer T, Wurm K, Schlaak M, Müller‐Quernheim J, Schwinger E (2001). Angiotensin‐converting enzyme (ACE) gene polymorphisms and familial occurrence of sarcoidosis. J Intern Med, 249:77-83.
Fløe A, Hoffmann HJ, Nissen PH, Møller HJ, Hilberg O (2014). Genotyping increases the yield of angiotensin-converting enzyme in sarcoidosis–a systematic review. Dan Med J, 61:A4815.
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| Issue | Vol 45 No 11 (2016) | |
| Section | Original Article(s) | |
| Keywords | ||
| Sarcoidosis ACE gene polymorphism Angiotensin converting enzyme | ||
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