Henoch-Schonlein Purpuralı Çocuklarda Angiotensin Konverting Enzim Gen Polimorfizmi

Abstract

Amaç: Henoch-Schönlein purpuralı HSP 54 çocukta anjiotensin konverting enzim ACE gen polimorfizminin hastalığın kliniği, prognozu ve klinik seyri ile olan ilişkisini araştırmak amacıyla ACE geninin insersiyon I ve delesyon D polimorfizmini araştırdık. Gereç ve Yöntem: Hasta kan örnekleri EDTA’lı tüpe alındı. Lökosit DNA’sı elde edilerek PCR yöntemiyle ACE I/D polimorfizmleri belirlendi. Bulgular: Hastaların tümünde ACE genotipleri II, ID ve DD’nin oranları sırasıyla % 4, % 74 ve % 22 olarak saptandı. Hastalar HSP nefriti olanlar n=14 , HSP’li ve hafif idrar bulguları olanlar n=18 ve böbrek tutulumu olmayanlar n=22 olmak üzere üç gruba ayrıldı. ACE genotipleri II, ID ve DD’nin dağılımları sırasıyla HSP nefritinde % 7, % 57, % 36; hafif idrar bulguları olanlarda % 0, % 89, % 11; böbrek tutulumu olmayanlarda % 5, % 72, % 23 olarak saptandı. Renal tutulum varlığı ile ACE genotipleri arasında istatistiksel olarak anlamlı bir ilişki saptanmadı χ2 =4.39, p=0.356 . ACE allelleri I ve D’nin dağılımları sırasıyla HSP nefritinde % 36 ve % 64, hafif idrar bulguları olanlarda % 44 ve % 56, böbrek tutulumu olmayanlarda ise % 41 ve % 59 olarak saptandı. Böbrek tutulumu ile ACE allelleri arasında istatistiksel olarak anlamlı bir ilişki saptanmadı χ2 =0.500, p=0.780 . Sonuç: Bu veriler HSP’li çocuklarda böbrek tutulumu ile DD genotipi veya D alleli arasında istatistiksel olarak anlamlı bir ilişkiyi desteklememektedir. Bununla birlikte D alleli hastaların % 96’sında saptandı ve DD genotipi de HSP nefritli hastalarda böbrek tutulumu olmayanlara göre daha yüksek bulundu. Bu sonuçlara göre hastalığın oluşumunda ve renal tutulumda D allelinin kolaylaştırıcı ve I allelinin ise koruyucu faktör olduğunu gösterdik, fakat bu bulguları destekleyen daha büyük çalışmalar gereklidir.

Keywords

• ACE gen polimorfizmi,HenochSchönlein purpursı

Angiotensin Converting Enzyme Gene Polymorphism in Children with Henoch-Schonlein Purpura

Abstract

Objective: We examined the insertion I and deletion D polymorphism of angiotensin converting enzyme ACE gene polymorphism in 54 children with HSP to investigate the associated with presentation, prognosis and progression of children with Henoch-Schönlein purpura HSP . Materal and Methods: Blood samples were collected from patients and obtained into EDTA. Genomic DNA from peripheral blood lymphocytes was purified. The ACE I/D gene polymorphism was detected by PCR with primer sequences derived. Results: The percent of ACE genotypes II, ID and DD in all patients was detected 4 %, 74 % and 22 % respectively. Patients were divided into 3 groups as HSP nephritis n=14 , HSP with minor urinary anomaly n=18 and HSP without renal involvement n=22 . The distribution of ACE genotypes II, ID and DD respectively in HSP nephritis was 7 %, 57 %, 36 %; in HSP with minor urinary anomaly was 0 %, 89 %, 11 %; and in HSP without renal involvement was 5 %, 72 %, 23 % detected. No association was found between the ACE genotypes and the presence of renal involvement χ2 =4.39, p=0.356 . The distribution of ACE allels I and D respectively in HSP nephritis was 36 % and 64 %; in HSP with minor urinary anomaly was 44 % and 56 % and in HSP without renal involvement was 41 % and 59 % detected. No association was found between the ACE allels and the presence of renal involvement χ2 =0.500, p=0.780 . Conclusion: In conclusion these results does not support a statistically significantly association between renal involvement and DD genotype or D allel in children with HSP. However D allele was detected in 96 % patients and DD genotype was higher in patients with HSP nephritis than patients without renal involvement. According these results we showed that D allel is a facilitative and I allel is a protective factor for development and renal involvement of disease. However larger studies are required to confirm these results.

Keywords

• ACE gene polymorphism,Henoch-Schönlein purpura

References

1. 1. Jennette JC, Falk RJ, Andrassy K, Bacon PA, Churg J, Gross WL, Hagen EC, et al. Nomenclature of systemic vasculitides. Proposal of an international consensus conference. Arthritis Rheum 1994;37:187-92. http://dx.doi.org/10.1002/art.1780370206 PMid:8129773
2. 2. Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion deletion polymorphism in the angiotensin I converting enzyme gene accounting for half of the variance of serum enzyme levels. J Clin Invest 1990;86:1343-6. http://dx.doi.org/10.1172/JCI114844 PMid:1976655 PMCid:296868
3. 3. Iwai N, Ohmichi N, Nakamura Y, Kinoshita M. DD genotype of the angiotensin- converting enzyme gene is a risk factor for left ventricular hypertrophy. Circulation 1994;90:2622-8. http://dx.doi.org/10.1161/01.CIR.90.6.2622 PMid:7994801
4. 4. Dorria A, Warram JH, Krowlewski AS. Genetic predisposition to diabetic nephropathy: evidence for a role of the angiotensin I converting enzyme gene. Diabetes 1994;43:690-5. http://dx.doi.org/10.2337/diabetes.43.5.690
5. 5. Lee DY, Kim W, Kang SK, Koh GY, Park SK. Angiotensinconverting enzyme gene polymorphism in patients with minimal change nephrotic syndrome and focal segmental glomerulosclerosis. Nephron 1997;77:471-3. http://dx.doi.org/10.1159/000190326 PMid:9434071
6. 6. Harden PN, Geddes C, Rowe PA, McIlroy JH, BoultonJones M, Rodger RS. Polymorphisms in angiotensinconverting enzyme gene and progression of IgA nephropathy. Lancet 1995;345:1540-1. http://dx.doi.org/10.1016/S0140-6736(95)91088-3
7. 7. Tatsuma N, Asano T, Yoshida J, Ohashi R, Munakata E, Ambo K, Tsuchiya M. Angiotensin converting enzyme gene polymorphism with nephritis of Henoch-Schonlein purpura (abstract). Pediatr Nephrol 1998;12:C123.
8. 8. Yoshioka T, Xu Y, Yoshida H, Shiraga H, Muraki T, Ito K. Deletion polymorphism of angiotensin converting enzyme gene predicts persistent proteinuria in Henoch-Schonlein purpura nephritis. Arch Dis Child 1998;79:394-9. http://dx.doi.org/10.1136/adc.79.5.394 PMid:10193250 PMCid:1717731

9. 9. Ozkaya O, Soylemezoglu O, Gonen S, Misirlioglu M, Tuncer S, Kalman S, Buyan N. Renin-angiotensin system gene polymorphisms: association with susceptibility to Henoch-Schonlein purpura and renal involvement. Clin Rheumatol 2006;25:861-5. http://dx.doi.org/10.1007/s10067-006-0207-4 PMid:16521052
10. 10. Amoroso A, Danek G, Vatta S, Crovella S, Berrino M, Guarrera S, Fasano ME, Coppo R and Behalf of the Italian Group of Renal Immunopathology. Polymorphism in angiotensin-converting enzyme gene and severity of renal disease in Henoch-Schonlein patients. Nephrol Dial Transplant 1998;13:3184-8. http://dx.doi.org/10.1093/ndt/13.12.3184 PMid:9870486
11. 11. Mills JA, Michel BA, Block D. The Americal College of Rheumatology 1990 criteria for the classification of HenochSchonlein Purpura. Arthritis Rheum 1990;33:1114-21. http://dx.doi.org/10.1002/art.1780330809 PMid:2202310
12. 12. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1998;16:1215-20. http://dx.doi.org/10.1093/nar/16.3.1215
13. 13. Zee RY, Lou YK, Griffiths LR, Morris BJ. Association of a polymorphism of the angiotensin I-converting enzyme gene with essential hypertension. Biochem Biophys Res 184:9-15.
14. 14. Haszon I, Friedman AL, Papp F, Bereczki C, Baji S, Bodrogi T. ACE gene polymorphism and renal scarring in primary vesicoureteric reflux. Pediatr Nephrol 2002;17: 1027-31. http://dx.doi.org/10.1007/s00467-002-0968-1 PMid:12478352
15. 15. Hohenfellner K, Hunley TE, Brezinska R, Brodhag P, Shyr Y, Brenner W. ACE I/D gene polymorphism predicts renal damage in congenital uropathies. Pediatr Nephrol 1999;13: 514-8. http://dx.doi.org/10.1007/s004670050649 PMid:10452281
16. 16. Ozen S, Alikasifoglu M, Tuncbilek E, Bakkaloglu A, Besbas N, Aran B, Saatci U. Polymorphism in angiotensin converting enzyme gene and reflux nephropathy: a genetic predisposition to scar formation. Nephrol Dial Transplant 1997; 12:2031-2. http://dx.doi.org/10.1093/oxfordjournals.ndt.a027788 PMid:9306373