Gene polymorphism of angiotensine-converting enzyme in glomerulonephritis

Aim. The frequency distribution of gene polymorphism of angiotensin-converting enzyme (АCE) and its correlation with ACE activity in kyrgyz population with glomerulonephritis (GN) were studied. Material and methods. 48 GN patients 34,08 ± 1,9 years old and 48 healthy subjects were studied. A polymorphic site of ACE gene was amplified using polymerize chain reaction (PCR). ACE concentration and its activity were defined spectrofluorimetrically. Results. The distribution of genotypes II, ID and DD of ACE gene among the patients with GN and in control group corresponded to the Hardi-Wainberg distribution: II - 20,8% (n = 10), ID - 66,7% (n = 32), DD - 12,5% (n = 6), allele I - 54,1%, allele D - 45,9% in patients with GN, and II - 33,3% (n = 16), ID - 52,1% (n = 25), DD - 14,6% (n = 7), allele I - 59,3%, allele D - 40,7% in control group. However, no significant difference in frequency of genotypes and alleles in the specified groups was revealed (χ2 = 2,3; p > 0,05). The average values of АCE activity (ng/ml) in the patients with GN for each of genotypes II, ID and DD were 25,05 ± 3,38, 31,81 ± 2,28 and 41,25 ± 5,65, respectively. Their average value in control group was 23,68 ± 0,99, 31,4 ± 1,73 and 38,06 ± 4,45, respectively. Thus, АCE activity in patients with GN was much higher at DD-genotype in comparison with II-genotype (р < 0,02). In control group the АCE activity was much higher in the subjects with DD-genotype compared to that in patients with II-genotype and ID-genotype (р < 0,02). The total cholesterol level in patients with GN with DD-genotype (7,74 ± 1,16 mmol/l) was significantly higher than in patients with II- (4,69 ± 0,36 mmol/l) and ID- (5,09 ± 0,36 mmol/l) genotypes (р < 0,05). Conclusion. Development of CGN doesn’t associate with ACE gene polymorphism in kyrgyz population. At the same time activity of ACE is much higher at the patients with CGN and in healthy persons with genotype DD. It’s related with higher concentration of cholesterol in the serum.

полиморфизм, ген, ангиотензин-превращающий фермент, гломерулонефрит, холестерин

1. Кутырина И.М., Тареева И.Е., Носиков В.В. и др. Изучение полиморфизма гена ангиотензин-превращающего фермента при хроническом гломерулонефрите. Тер. арх. 1999; 6: 94-96.

2. Cambien F., Poirier O., Lecerf L. et al. Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 1992; 359: 641-644.

3. Costerouse O., Allegrini J., Lopez M., Alhenc-Gelas F. Angiotensin I Converting enzyme in human circulating mononuclear cells: Genetic polymorphism of expression in T-lymphocyte. Biochem J 1993; 290: 33-40.

4. Krege J.K., Kim H.C., Moyer J.S. et al. Angiotensin converting enzyme gene mutations, blood pressure and cardiovascular homeostasis. Hypertension 1997; 29: 150-157.

5. Lau Y.K., Woo K.T., Choong H.L. et al. ACE gene polymorphism and disease progression of IgA Nephropathy in Asians in Singapore. Nephron 2002; 91: 499-503.

6. Losito A., Kalidas K., Santoni S. et al. Polymorphism of renin-angiotensin system genes in dialysis patients - association with cerebrovascular disease. Nephrol Dial Transplant 2002; 17: 2184-2188.

7. Matsubara M., Suzuki M., Kikuya M. et al. Angiotensin converting enzyme I/D polymorphism and hypertension: The Ohasama study. J of Hypertension 2002; 20: 1121-1126.

8. Navis G., Van Der Kleij F.G., De Zeeuw D., De Jong P.E. Angiotensin-Converting enzyme gene polymorphism has no influence on the circulating renin-angiotensin-aldosterone system or blood pressure in normotensive subjects. Circulation 1995; 91: 2933-2942.

9. Ong-Ajyooth S., Ong-Ajyooth L., Limmongkon A. et al. The renin-angiotensin system gene polymorphisms and clinicopathological correlations in IgA nephropathy. J Med Assoc Thai 1999; 82: 681-689.

10. Rigat B., Hubert C., Alhenc-Gelas F. et al. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990; 86: 1343-1346.

11. Schena F.P., D’Altri C., Cerullo G. et al. ACE gene polymorphism and IgA nephropathy: An ethnically homogeneous study and a meta-analysis. Kidney Int 2001; 60: 732-740.

12. Stefansson B., Ricksten A., Rymo L. et al. Angiotensin-converting enzyme gene I/D polymorphism in malignant hypertension. Blood Press 2000; 9: 1054-1059.

13. Tiret L., Rigat B., Visvikis S. et al. Evidence from combined segregation and linkage analysis, that a variant of the angiotensin-converting enzyme ACE gene controls plasma levels. Amer J Hum Genet 1992; 51: 197-205.

14. Van der Kleij F.G.H., De Jong P.E., Henning R.H. et al. Enhanced responses of blood pressure, renal function and Aldosterone to angiotensin I in the DD genotype are blunted by low sodium intake. J Am Soc Nephrol 2002; 13: 1025-1033.