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TÜRK TİP 2 DİABETİK HASTA POPULASYONUNDA ANJİOTENSİN DÖNÜŞTÜRÜCÜ ENZİM POLİMORFİZMİNİN DİABETİK NEFROPATİ VE DİĞER VASKÜLER KOMPLİKASYONLAR İLE İLİŞKİSİ

RELATIONSHIP BETWEEN ANGIOTENSIN CONVERTING ENSYME POLYMORPHISM AND DIABETIC NEPHROPATHY AND OTHER VASCULAR COMPLICATIONS IN TURKISH PATIENTS WITH TYPE 2 DIABETES MELLİTUS

Journal Name:

  • Türk Nefroloji, Diyaliz ve Transplantasyon Dergisi

Publication Year:

  • 2003

Keywords (Original Language):

Author NameUniversity of AuthorFaculty of Author
Abstract (2. Language): 
Cardiovascular disease and diabetic nephropahty account for much of the morbidity and mortality associated with diabetes mellitus. Genotypic abnormalities of the renin-angiotensin system have been suggested as a risk factor for the development of diabetic complications. We studied the relationship between an insertion(I)/deletion(D) polymorphism in angiotensin converting enzyme (ACE) gene in non-insulin dependent diabetes mellitus (NIDDM) patients with various diabetic complications. We examined 159patients (Mean age 58.1 ±12.1 years) with NIDDM of more than 3 years duration. (Mean duration of diabetes; 11.7+8 years). As control we took 44 healthy volunteers (Mean age 55.3+9.9years). The 1/Dpolymorphism was analyzed with PCR technique and alleles were visualized on %2 agarose gels after ethidium staining. Distribution of genotypes was not significantly different NIDDM patients with and without nephropathy , hypertension, retinopathy, neuropathy. The DD genotype was found to be related with peripheral arterial diseases (P=0.05). ID genotype was related with ischemic heart disease (P=0.03) and cardiomyopathy (P=0.05). No significant gender difference was found between II/ID/DD genotypes and I/D alleles. Serum glucose (P=0.02) and HbAlc (p=0.005) values were significantly high in II genotyped patients. No genotype correlation was found between diabetes and complications in relatives of the patients (P>0.05). In conclusion there is no significant association between DD/ID/ll genotypes of ACE gene in NIDDM patients with various degrees of diabetic nephropathy (P>0.05). Only patients with diabetic nephropathy who were on renal replacement therapy had D allele more than other diabetic patients and control subjects. Though there is no correlation with diabetic nephropathy ACE gene polymorphism DD and ID genotypes can be a notable genetic marker for cardiovascular and peripheral arterial disease. Follow-up studies is needed to achieve a better understanding of the role of candidate gene polymorphisms on the development of complications of NIDDM.
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Abstract (Original Language): 
Diabetes Mellitusla ilgili morbidite ve morlaliteden daha çok kardiovasküler hastalıklar ve diabetik nefropati sorumlu tutulmaktadır. Renin-anjitensin sisteminin genotipik anormallikleri diabetik komplikasyonlann gelişmesinde risk faktörü olarak kabul edilmektedir. Biz. çeşitli diabetik komplikasyonlan olan insuline bağımlı olmayan diabetes mellituslu (NIDDM) hastalarda anjiotensin konverting enzim (ACE) genindeki insersiyon (l)Zdelesyon (D) polimorfizmlerinin ilişkisini çalıştık. 3 yıldan daha uzun süreli NIDDM ile izlenen 159 hastayı (Ort. Yaş 58,1 ±12,1 yıl) inceledik. (Ortalama diabel sürelesi; 11,7+8 yıl). Kontrol grubu olarak 44 sağlıklı gönüllü (Ort.Yaş 55,3+9,9) aldık. l/D polimorfizmi PCR tekniği ile incelendi ve alleller ethidium boyamasından sonra %2'lik agar jel ile gösterildi. Diabetik nefropatisi, hipertansiyonu, retinopatisi ve nöropatisi olan ve olmayan NÎDDM'lilerde genotip dağılımında fark yoktu (P>0,05). DD genotipinin periferik arter hastalığı ile ilişkili olduğu tespit edildi (P=0,05). İD genotipi iskemik kalb hastalığı (P=0,03) ve kardiomyopati (P=0,05) ile ilişkiliydi. II/ID/DD genotipleri ve l/D atletlerinin cinsiyet açısından aralarında anlamlı fark yoktu(P>0,05). II genotipindeki hastaların serum glukoz (P=0,02) ve HbAlc (P=0,005) değerlerinin anlamlı olarak yüksek olduğu bulundu. Ailede diabet ve diabet komplikasyonlan ile hiçbir genotip korelasyonu bulunmadı (P>0,05). Sonuç olarak; çeşitli düzeylerde diabetik nefropatisi olan NIDDM'li hastalarda ACE geninin DD/ID/1I genotipleri ile ilişki yoktur (P>0,05). Sadece renal replasman tedavisindeki hastalarda diğer diabetikler ve kontrol grubuna göre daha fazla olarak D alleli tespit edildi. ACE gen polimorfiz.minin diabetik nefropati ile ilişkisi olmamasına rağmen DD ve İD genotipleri kardiovasküler ve periferik arter hastalığı için iyi birer genetik marker olabilir. Aday genlerin NIDDM komplikasyonlan polimorfizmlerinin rollerinin anlaşılabilmesi için izlem çalışmalarına ihtiyaç vardır.
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  • Turkish

REFERENCES

References: 

1) Türk Nefroloji Derneği Registry 2001.Türk Nefroloji Derneği Yayınları.
2) Erdös E. Skidgel R.A, The angiotensin I-converting
enzyme. Lab invest 1987;56:345-348
3) Luetscher JA, Kraemer FB, Wilson DM, Schwartz HC, Bryerash M. Increased plasma inactive renin in diabetes mellitus: A marker of microvascular complications. N Engl J Med 1985;312:1412-1417
4) Schmidt S, Schöne N, Ritz E and the Diabetic
Nephropathy Study Group. Assosiation of ACE gene polymorphism and diabetic nephropathy?: Kidney Int 1997;47:1176-1181
5) Egido J. Vasoactive hormones and renal sclerosis. (Perspectives in Clinical Nefrology): Kidney Iht 1996; 49: 578-597
6) Alhenc-Gelas F, Richard J, Courbon D, Warnet JM, Corvol P. Distribution of plasma angiotensin 1-converting enzyme levels in healthy men: Relationship to environmental and hormonal parameters. J Lab Clin Med 1991;117:33-39
7) Graham DE. The isolation of high molecular weight DNA from whole organisms or large tissue masses.
Annal Biochem 1978;85:609-613
8) Miller SA, Dykes DD, Polesky HF. A simple salting
out procedure for extracting DNA from human
nucleated cells. Nucl Acids Res. 1988;16:1215
9) Ballard DJ, Humphrey LL, Melton LJ et al.
Epidemiology of persistent proteinuria in type II
diabetes mellitus. Diabetes 1988;37:405-412
10) Sawicki PT, Kaiser S, Ehle B, Frenzel H, Berger M. Post mortem Unter-suchung zur Haufigkeit von Nierenarterienstensen bei Paienten mit Diabetes
Mellitus. Akt Endokrinologie Stoffe 1989;10.i25a
11) Deferrari G, Cheli V, Robaudo C. Treatment of diabetic
nephropaty in its early stages. Diabetes Metab Rev 1997;13:51-61
12) Freedman BI, Tuttle AB, Spray BJ. Familial predisposition to nephropathy in African-Americans with non-insulin dependent diabetes mellitus. Am J
Kidney Dis 1995;25:710-713
13) Seaquist ER, Goetz FC, Rich S, Barbosa J. Familial clustering of diabetic kidney disease. N Engl J Med 1989;320:1161-1165
14) Allen TJ, Cooper ME, Gilbert RE, Winikoff J, Skinner
SL, Jerums G: Serum total renin is increased before microalbuminuria in diabetes. Kidney Int 1996;50:902-
907
15) Hallab M, Bled F, Ebran JM, Suraniti S, Girault A,
Fressinaud PH, Marre M. Elevated serum angiotensin converting enzyme activity in type I, insulin-dependent diabetic subjects with persistent microalbuminuria.
ActaDiabetol 1992;29:82-85
16) Schmidt S, Ritz E. Genetics of the renin-angiotensin system and renal disease: A progress report. (Review)
Curr Opin Nephrol Hypertens 1997;6:146-151
13
17) Anderson S, Rennke HG, Brenner BM. Therepeutic advantage of converting enzyme inhibitors in arresting progressive renal disease associated with systemic
hypertension. J Clin Invest 1986;77:1993-2000
18) Nakai K, Itoh C, Miura Y. Deletion polymorphism of the angiotension I convertig enzyme gene is associated with serum ACE concentration and increased risk for CAD in Japanese population. Circulation 1995;91: 2199-2202
19) Reynolds MV, Bristow MR, Bush EW et al. ACE DD
genotype in patients with ischemic or idiopathic dilated
cardiopathy. Lancet 1993;342:1073-1075
20) Schunkert H, Hense HW, Holmer SR et al. Assosiation between a deletion polymorphism of ACE gene and left
ventricular hypertrophy. NEJM 1994; 1634-163 8
21) Naoharu I, Nobuyuki O et al. DD genotype of the ACE gene is a risk factor for left ventricular hypertrophy.
Circulation 1994;90:20622-20628
22) Perticone F, Cervolo R, Cosco C et al. Deletion polymorphism of ACE gene and left ventricular hypertrophy in Southern Italian patients. JACC 1997; 29:365-369
23) Ohishi M, Fujii K. A potent risk factor for restenosis.
Nature Gen 1993;5:324-325
24) Freire M, Dijk D, Erman A, Boner G, Warram J, Krolewski A. DNA polymorphism in the ACE gene, serum ACE activity and risk of nephropathy in insulin-dependent diabetes mellitus. Nephrol Dial Transplant 1998;13:2553-2558
25) Mizuiri S, Yoshikawa H, Tanegashiwa, Miyagi M et al. Renal ACE Immunohisto- chemical localization in NIDDM patients with nephropathy. Am J Kidney Dis 1998;31:301-307
26) Schmidt S, Schöne N, Ritz E and the Diabetic
Nephropathy Study Group. Assosiation of ACE gene polymorphism and diabetic nephropathy? Kidney Int
1997;47:1176-1181
27) Marre M, Bernadet P, Gallois Y, Savagner F et al. Relationship between angiotensin I converting enzyme gene polymorphism, plasma leves, and diabetic retinal and renal complications. Diabetes 1994;43:384-388
28) Akar N, Araş O, Omurlu K, Cin S. Deletion
polymorphism at the angiotensin-converting enzyme gene in Turkish patients with coronary artery disease.
Scand J Clin Lab Invest 1998;58(6):491-495
29) Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol
P, Soubrier F. An insertion/deletion poli morphism in the Angiotensin 1-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin
Invest 1990;86:1343-1346
30) Tiret L, Rigat B, Visvikis S, et al. Evidence from combined segregation and linkage analysis that a variant of the angiotensin I converting enzyme (ACE) gene controls plasma ACE. Am J Hum Genet 1992;51: 197-205
31) Chiu KC, Me Carthy JE; The insertion allele at the angiotension I-converting enzyme gene locus is associated with insulin resistance. Metabolism: Clinical
and Experimental 1997;46(4):395-399
32) Staessen JA, Wong JG, Ginocchio G, Petrov V,
Saavedia AP, Soubrier F, Vlientinck R, Fogard R. The deletion/insertion polymorphism of the angiotensin
converting enzyme gene and cardiovascular-renal risk.
J Hypertension 1997; 15(12Pt2): 1579-1592
33) Doria A, Warram JH, Krolewski AS. Genetic predisposition to diabetic nephro-pathy. Evidence for a role of the angiotensin 1-converting enzyme gene.
Diabetes 1994;43:690-695
34) Morris AD, Petrie JR, Ueda S, et al Pressor and subpressor doses of angiotensin II increase insulin sensitivity in NIDDM. Dissociation of metabolic and blood pressure effects. Diabetes 1994:43(12): 1445¬1449
35) Azar ST. Zalloua PA, Medlej R, Halabi G. The
genotype of the ACE gene polymorphism is associated with diabetic nephropathy in type-1 diabetics. Endocr
Res2001;27(l-2):99-108
36) Hosoi M, Nishizawa Y, Kogawa K, Kawagishi T, et al Angiotensin converting enzyme gene polymorphism is associated with carotid arterial wall thickness in non-insulin dependent diabetic patients. Circulation 1996; 94(4):704-707
37) Ohno T, Kawazu S, Tomono S. Association analysis of the polymorphism of angiotensin-converting enzyme and Japanase non-insulin dependent diabetics. Metabolism: Clinical and Experimental 1996;45(2): 218-222
38) Jeffers BW, Estacio RO, Raynolds MV, Schrier RW.
Angiotensin-converting enzyme gene polymorphism in non-insulin dependent diabetes mellitus and its relationship with diabetic nephropathy. Kidney Int 1997;52(2):473-477
39) Nakajima S, Baba T, Yajima Y. Is ACE gene polymorphism a useful marker for diabetic albuminuria in Japanese NIDDM patients? Diabetes Care 1996; 19 (12):1420-1422
40) Cambien F, Poirrier O, Lecerf, et al. Deletion polymorphysim in the gene for ACE is potent risk factor for myocardial infarction. Nature 1992; 359: 641-644
41) Schunkert H, Hense HW, Holmer SR et al. Assosiation between a deletion polymorphism of ACE gene and
left ventricular hypertrophy. NEJM 1994; 1634-1638
42) Yıldız A, Akkaya V, Hatemi et al, No association between deletion-type angiotensin-converting enzyme gene polymorphism and left-ventricular hypertrophy in
hemodialysis patients. Nephron. 2000;84(2): 130-5.
43) Beohar N, Damaraju S, Prather A, et al. Angiotensin I-converting enzyme genotype DD is a risk factor for coronary artery disease. J Invest Med. 1995;43(3):275-
280
44) Doi Y, Yoshizumi H, Yoshinari M et al, Association between a polymorphism in the angiotensin converting enzyme gene and microvascular complications in Japanese patients with NIDDM: Diabetologia 1996;39
(l):97-102
45) Fujisawa T, Ikegami H, Kawaguchi Y et al, Meta-analysis of association of insertion/deletion polymorphism of angiotensin I-converting enzyme gene with diabetic nephropathy and retinopathy.
Diabetologia 1998;41(l):47-53
14
46) Chiu KC, Me Carthy JE: The insertion allele at the angiotension I-converting enzyme gene locus is associated with insulin resistance. Metabolism: Clinical and Experimental 1997; 46(4): 395-399
47) Panahloo A, Andres C, Mohamed-Ali V et al, The
insertion allele of the ACE gene I/D polymorphism. A candidate gene for insulin resistance? Circulation 1995; 92(12): 3390-3393
48) Buchanan TA, Thawani H, Kades W et all, Modrall JG; W. Angiotensin II increases glucose utization during acute hyperinsulinemia via a hemodynamic mechanism.
Journal of Clinical Invest 1993; 92(2): 720-726
49) Morris AD, Petrie JR, Ueda S et al, Subpressor doses of angiotensin II increase insulin sensitivity in NIDDM. Dissociation of metabolic and blood pressure effects.
Diabetes 1994; 43(12): 1445-1449
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