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Diabetologia

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01.05.2005 | Article

Angiotensin-I converting enzyme insertion/deletion polymorphism and its association with diabetic nephropathy: a meta-analysis of studies reported between 1994 and 2004 and comprising 14,727 subjects

verfasst von: D. P. K. Ng, B. C. Tai, D. Koh, K. W. Tan, K. S. Chia

Erschienen in: Diabetologia | Ausgabe 5/2005

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Abstract

Aims/hypothesis

The ACE insertion/deletion polymorphism has been examined for association with diabetic nephropathy over the past decade with conflicting results. To clarify this situation, we conducted a comprehensive meta-analysis encompassing all relevant studies that were published between 1994 and 2004 and investigated this potential genetic association.

Methods

A total of 14,727 subjects from 47 studies was included in this meta-analysis. Cases (n=8,663) were type 1 or 2 diabetic subjects with incipient (microalbuminuria) or advanced diabetic nephropathy (proteinuria, chronic renal failure, end-stage renal disease). Control subjects (n=6,064) were predominantly normoalbuminuric.

Results

No obvious publication bias was detected. Using a minimal-case definition based on incipient diabetic nephropathy, subjects with the II genotype had a 22% lower risk of diabetic nephropathy than carriers of the D allele (pooled odds ratio [OR]=0.78, 95% CI=0.69–0.88). While there was a reduced risk of diabetic nephropathy associated with the II genotype among Caucasians with either type 1 or type 2 diabetes, the association was most marked among type 2 diabetic Asians (Chinese, Japanese, Koreans) (OR=0.65, 95% CI=0. 51–0.83). This OR is significantly different from the OR of 0.90 (95% CI= 0.78–1.04) that was obtained for type 2 diabetic Caucasians (p=0.019). Using a stricter case definition based on advanced diabetic nephropathy, a comparable risk reduction of 24–32% was observed among the three subgroups, although statistical significance was reached only among Asians.

Conclusions/interpretation

The results of our meta-analysis support a genetic association of the ACE Ins/Del polymorphism with diabetic nephropathy. These findings may have implications for the management of diabetic nephropathy using ACE inhibitors especially among type 2 diabetic Asians.

National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD. US (2003) Renal data system annual data report: atlas of end-stage renal disease in the United States

Singapore Renal Registry (1997) First report of the Singapore Renal Register

Lewis EJ, Hunsicker LG, Bain RP, Rohde RD (1993) The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med 329:1456–1462CrossRefPubMed

Jacobsen P, Rossing K, Rossing P et al (1998) Angiotensin converting enzyme gene polymorphism and ACE inhibition in diabetic nephropathy. Kidney Int 53:1002–1006

Penno G, Chaturvedi N, Talmud PJ et al (1998) Effect of angiotensin-converting enzyme (ACE) gene polymorphism on progression of renal disease and the influence of ACE inhibition in IDDM patients: findings from the EUCLID Randomized Controlled Trial. EURODIAB Controlled Trial of Lisinopril in IDDM. Diabetes 47:1507–1511

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

Krolewski AS, Ng DPK, Canani LH, Warram JH (2001) Genetics of diabetic nephropathy: how far are we from finding susceptibility genes? Adv Nephrol Necker Hosp 31:295–315PubMed

Marre M, Bernadet P, Gallois Y et al (1994) Relationships between angiotensin I converting enzyme gene polymorphism, plasma levels, and diabetic retinal and renal complications. Diabetes 43:384–388

Tarnow L, Gluud C, Parving HH (1998) Diabetic nephropathy and the insertion/deletion polymorphism of the angiotensin-converting enzyme gene. Nephrol Dial Transplant 13:1125–1130

10.

Kunz R, Bork JP, Fritsche L et al (1998) Association between the angiotensin-converting enzyme-insertion/deletion polymorphism and diabetic nephropathy: a methodologic appraisal and systematic review. J Am Soc Nephrol 9:1653–1663PubMed

11.

Fujisawa T, Ikegami H, Kawaguchi Y et al (1998) Meta-analysis of association of insertion/deletion polymorphism of angiotensin I-converting enzyme gene with diabetic nephropathy and retinopathy. Diabetologia 41:47–53

12.

Doria A, Warram JH, Krolewski AS (1994) Genetic predisposition to diabetic nephropathy. Evidence for a role of the angiotensin I-converting enzyme gene. Diabetes 43:690–695

13.

Powrie JK, Watts GF, Ingham JN et al (1994) Role of glycaemic control in development of microalbuminuria in patients with insulin dependent diabetes. BMJ 309:1608–1612

14.

Dudley CR, Keavney B, Stratton IM et al (1995) UK prospective diabetes study: XV. Relationship of renin–angiotensin system gene polymorphisms with microalbuminuria in NIDDM. Kidney Int 48:1907–1911

15.

Fujisawa T, Ikegami H, Shen GQ et al (1995) Angiotensin I-converting enzyme gene polymorphism is associated with myocardial infarction, but not with retinopathy or nephropathy, in NIDDM. Diabetes Care 18:983–985

16.

Mizuiri S, Hemmi H, Inoue A et al (1995) Angiotensin-converting enzyme polymorphism and development of diabetic nephropathy in non-insulin-dependent diabetes mellitus. Nephron 70:455–459

17.

Panagiotopoulos S, Smith TJ, Aldred GP et al (1995) Angiotensin-converting enzyme (ACE) gene polymorphism in type II diabetic patients with increased albumin excretion rate. J Diabetes Complicat 9:272–276

18.

Schmidt S, Schone N, Ritz E (1995) Association of ACE gene polymorphism and diabetic nephropathy? The Diabetic Nephropathy Study Group. Kidney Int 47:1176–1181

19.

Tarnow L, Cambien F, Rossing P et al (1995) Lack of relationship between an insertion/deletion polymorphism in the angiotensin I-converting enzyme gene and diabetic nephropathy and proliferative retinopathy in IDDM patients. Diabetes 44:489–494PubMed

20.

Rabensteiner D, Mayer G, Abrahamian H et al (1995) Relationship between angiotensin-I-converting enzyme polymorphism and microangiopathy in IDDM subjects. Diabetologia 38(Suppl):A227

21.

Chowdhury TA, Dronsfield MJ, Kumar S et al (1996) Examination of two genetic polymorphisms within the renin–angiotensin system: no evidence for an association with nephropathy in IDDM. Diabetologia 39:1108–1114

22.

Doi Y, Yoshizumi H, Yoshinari M et al (1996) Association between a polymorphism in the angiotensin-converting enzyme gene and microvascular complications in Japanese patients with NIDDM. Diabetologia 39:97–102

23.

Nakajima S, Baba T, Yajima Y (1996) Is ACE gene polymorphism a useful marker for diabetic albuminuria in Japanese NIDDM patients? Diabetes Care 19:1420–1422

24.

Oh TG, Shin CS, Park KS et al (1996) Relationship between angiotensin I converting enzyme gene polymorphism and renal complications in Korean IDDM patients. Korean J Intern Med 11:133–137

25.

Ohno T, Kawazu S, Tomono S (1996) Association analyses of the polymorphisms of angiotensin-converting enzyme and angiotensinogen genes with diabetic nephropathy in Japanese non-insulin-dependent diabetics. Metabolism 45:218–222

26.

Yoshida H, Kuriyama S, Atsumi Y et al (1996) Angiotensin I converting enzyme gene polymorphism in non-insulin dependent diabetes mellitus. Kidney Int 50:657–664

27.

Barnas U, Schmidt A, Illievich A et al (1997) Evaluation of risk factors for the development of nephropathy in patients with IDDM: insertion/deletion angiotensin converting enzyme gene polymorphism, hypertension and metabolic control. Diabetologia 40:327–331

28.

Gutierrez C, Vendrell J, Pastor R et al (1997) Angiotensin I-converting enzyme and angiotensinogen gene polymorphisms in non-insulin-dependent diabetes mellitus. Lack of relationship with diabetic nephropathy and retinopathy in a Caucasian Mediterranean population. Metabolism 46:976–980

29.

Hibberd ML, Millward BA, Demaine AG (1997) The angiotensin I-converting enzyme (ACE) locus is strongly associated with age and duration of diabetes in patients with type I diabetes. J Diabetes Complicat 11:2–8

30.

Jeffers BW, Estacio RO, Raynolds MV, Schrier RW (1997) Angiotensin-converting enzyme gene polymorphism in non-insulin dependent diabetes mellitus and its relationship with diabetic nephropathy. Kidney Int 52:473–477

31.

Marre M, Jeunemaitre X, Gallois Y et al (1997) Contribution of genetic polymorphism in the renin–angiotensin system to the development of renal complications in insulin-dependent diabetes: Genetique de la Nephropathie Diabetique (GENEDIAB) study group. J Clin Invest 99:1585–1595

32.

Pfohl M, Frost D, Koch M et al (1998) Lack of association between the insertion/deletion polymorphism of the angiotensin-converting-enzyme gene and diabetic nephropathy in IDDM patients. Horm Metab Res 30:276–280

33.

Ringel J, Beige J, Kunz R, et al (1997) Genetic variants of the renin–angiotensin system, diabetic nephropathy and hypertension. Diabetologia 40:193–199

34.

Demurov LM, Chistyakov DA, Chugunova LA et al (1997) Insertion/deletion of the angiotensin-converting enzyme gene in normalcy and among diabetics with vascular complications. Mol Biol 31:49–52

35.

Schmidt S, Strojek K, Grzeszczak W et al (1997) Excess of DD homozygotes in haemodialysed patients with type II diabetes. The Diabetic Nephropathy Study Group. Nephrol Dial Transplant 12:427–429

36.

Schmidt S, Ritz E (1997) Angiotensin I converting enzyme gene polymorphism and diabetic nephropathy in type II diabetes. Nephrol Dial Transplant 12(Suppl 2):37–41

37.

Freire MB, van Dijk DJ, Erman A et al (1998) DNA polymorphisms in the ACE gene, serum ACE activity and the risk of nephropathy in insulin-dependent diabetes mellitus. Nephrol Dial Transplant 13:2553–2558

38.

Grzeszczak W, Zychma MJ, Lacka B, Zukowska-Szczechowska E (1998) Angiotensin I-converting enzyme gene polymorphisms: relationship to nephropathy in patients with non-insulin dependent diabetes mellitus. J Am Soc Nephrol 9:1664–1669

39.

Hanyu O, Hanawa H, Nakagawa O et al (1998) Polymorphism of the angiotensin I-converting enzyme gene in diabetic nephropathy in type II diabetic patients with proliferative retinopathy. Ren Fail 20:125–133

40.

Huang XH, Rantalaiho V, Wirta O et al (1998) Angiotensin-converting enzyme insertion/deletion polymorphism and diabetic albuminuria in patients with NIDDM followed up for 9 years. Nephron 80:17–24

41.

Wu S, Xiang KS, Weng Q et al (1998) Relationship between angiotensin I converting enzyme gene polymorphism and diabetic nephropathy. Chin Med J 111:478–479

42.

Young RP, Chan JC, Critchley JA et al (1998) Angiotensinogen T235 and ACE insertion/deletion polymorphisms associated with albuminuria in Chinese type 2 diabetic patients. Diabetes Care 21:431–437

43.

Bouhanick B, Gallois Y, Hadjadj S et al (1999) Relationship between glomerular hyperfiltration and ACE insertion/deletion polymorphism in type 1 diabetic children and adolescents. Diabetes Care 22:618–622

44.

De Cosmo S, Margaglione M, Tassi V et al (1999) ACE, PAI-1, decorin and Werner helicase genes are not associated with the development of renal disease in European patients with type 1 diabetes. Diabetes/Metab Res Rev 15:247–253

45.

Kuramoto N, Iizuka T, Ito H et al (1999) Effect of ACE gene on diabetic nephropathy in NIDDM patients with insulin resistance. Am J Kidney Dis 33:276–281

46.

Miura J, Uchigata Y, Yokoyama H et al (1999) Genetic polymorphism of renin–angiotensin system is not associated with diabetic vascular complications in Japanese subjects with long-term insulin dependent diabetes mellitus. Diabetes Res Clin Pract 45:41–49

47.

Oue T, Namba M, Nakajima H et al (1999) Risk factors for the progression of microalbuminuria in Japanese type 2 diabetic patients—a 10 year follow-up study. Diabetes Res Clin Pract 46:47–55

48.

Tomino Y, Makita Y, Shike T et al (1999) Relationship between polymorphism in the angiotensinogen, angiotensin-converting enzyme or angiotensin II receptor and renal progression in Japanese NIDDM patients. Nephron 82:139–144

49.

Vleming LJ, van der Pijl JW, Lemkes HH et al (1999) The DD genotype of the ACE gene polymorphism is associated with progression of diabetic nephropathy to end stage renal failure in IDDM. Clin Nephrol 51:133–140

50.

Wong TY, Chan JC, Poon E, Li PK (1999) Lack of association of angiotensin-converting enzyme (DD/II) and angiotensinogen M235T gene polymorphism with renal function among Chinese patients with type II diabetes. Am J Kidney Dis 33:1064–1070

51.

Hsieh MC, Lin SR, Hsieh TJ et al (2000) Increased frequency of angiotensin-converting enzyme DD genotype in patients with type 2 diabetes in Taiwan. Nephrol Dial Transplant 15:1008–1013

52.

Van Ittersum FJ, de Man AM, Thijssen S et al (2000) Genetic polymorphisms of the renin–angiotensin system and complications of insulin-dependent diabetes mellitus. Nephrol Dial Transplant 15:1000–1007

53.

Tarnow L, Kjeld T, Knudsen E et al (2000) Lack of synergism between long-term poor glycaemic control and three gene polymorphisms of the renin angiotensin system on risk of developing diabetic nephropathy in type I diabetic patients. Diabetologia 43:794–799

54.

Araz M, Yilmaz N, Gungor K et al (2001) Angiotensin-converting enzyme gene polymorphism and microvascular complications in Turkish type 2 diabetic patients. Diabetes Res Clin Pract 54:95–104

55.

Azar ST, Zalloua PA, Medlej R, Halabi G (2001) The DD genotype of the ACE gene polymorphism is associated with diabetic nephropathy in the type-1 diabetics. Endocr Res 27:99–108

56.

Gohda T, Makita Y, Shike T et al (2001) Association of the DD genotype and development of Japanese type 2 diabetic nephropathy. Clin Nephrol 56:475–480

57.

Hadjadj S, Belloum R, Bouhanick B et al (2001) Prognostic value of angiotensin-I converting enzyme I/D polymorphism for nephropathy in type 1 diabetes mellitus: a prospective study. J Am Soc Nephrol 12:541–549

58.

Taniwaki H, Ishimura E, Matsumoto N et al (2001) Relations between ACE gene and ecNOS gene polymorphisms and resistive index in type 2 diabetic patients with nephropathy. Diabetes Care 24:1653–1660

59.

Viswanathan V, Zhu Y, Bala K et al (2001) Association between ACE gene polymorphism and diabetic nephropathy in South Indian patients. J Pancreas 2:83–87

60.

Araz M, Okan V, Celen Z, Aynacioglu S (2002) Angiotensin converting enzyme gene polymorphism and glomerular filtration rate changes in type 2 diabetic patients. Int J Clin Pract 56:416–418

61.

Fradin S, Goulet-Salmon B, Chantepie M et al (2002) Relationship between polymorphisms in the renin–angiotensin system and nephropathy in type 2 diabetic patients. Diabetes Metab 28:27–32

62.

De Azevedo MJ, Dalmaz CA, Caramori ML et al (2002) ACE and PC-1 gene polymorphisms in normoalbuminuric Type 1 diabetic patients: a 10-year prospective study. J Diabetes Complicat 16:255–262

63.

Lee YJ, Tsai JC (2002) ACE gene insertion/deletion polymorphism associated with 1998 World Health Organization definition of metabolic syndrome in Chinese type 2 diabetic patients. Diabetes Care 25:1002–1008PubMed

64.

Ha SK, Park HC, Park HS et al (2003) ACE gene polymorphism and progression of diabetic nephropathy in Korean type 2 diabetic patients: effect of ACE gene DD on the progression of diabetic nephropathy. Am J Kidney Dis 41:943–949

65.

Hadjadj S, Gallois Y, Alhenc-Gelas F et al (2003) Angiotensin-I-converting enzyme insertion/deletion polymorphism and high urinary albumin concentration in French Type 2 diabetes patients. Diabet Med 20:677–682

66.

Okuno S, Utsugi T, Ohno T et al (2003) Angiotensin-converting enzyme gene polymorphism as a potent risk factor for developing microalbuminuria in Japanese patients with type 2 diabetes mellitus: a 9-year follow-up study. J Int Med Res 31:290–298

67.

Ha SK, Seo JK (1997) Insertion/deletion polymorphism in ACE gene as a predictor for progression of diabetic nephropathy. Kidney Int 52 (Suppl 60):S28–S32

68.

Whitehead A (2002) Meta-analysis of controlled clinical trials. Wiley, Chichester, pp 197–213

69.

Fleiss JL (1993) The statistical basis of meta-analysis. Stat Methods Med Res 2:121–145PubMed

70.

Armitage P, Berry G (1994) Statistical methods in medical research, 3rd edn. Blackwell, London, p 521

71.

Araki S, Ng DP, Krolewski B et al (2003) Identification of a common risk haplotype for diabetic nephropathy at the protein kinase C-beta1 (PRKCB1) gene locus. J Am Soc Nephrol 14:2015–2024

72.

Mogensen CE, Christensen CK (1984) Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med 311:89–93PubMed

73.

Perkins BA, Ficociello LH, Silva KH et al (2003) Regression of microalbuminuria in type 1 diabetes. N Engl J Med 348:2285–2293

74.

Ellis D, Lloyd C, Becker DJ et al (1996) The changing course of diabetic nephropathy: low density lipoprotein cholesterol and blood pressure correlate with regression of proteinuria. Am J Kid Dis 27:809–818

75.

Ha SK, Lee SY, Park HS et al (2000) ACE DD genotype is more susceptible than ACE II and ID genotypes to the antiproteinuric effect of ACE inhibitors in patients with proteinuric non-insulin-dependent diabetes mellitus. Nephrol Dial Transplant 15:1617–1623

76.

Perna A, Ruggenenti P, Testa A et al (2000) ACE genotype and ACE inhibitors induced renoprotection in chronic proteinuric nephropathies. Kidney Int 57:274–281

77.

Keavney B, McKenzie CA, Connell JMC et al (1998) Measured haplotype analysis of the angiotensin-I converting enzyme gene. Hum Mol Genet 7:1745–1751

Titel: Angiotensin-I converting enzyme insertion/deletion polymorphism and its association with diabetic nephropathy: a meta-analysis of studies reported between 1994 and 2004 and comprising 14,727 subjects
verfasst von: D. P. K. Ng
B. C. Tai
D. Koh
K. W. Tan
K. S. Chia
Publikationsdatum: 01.05.2005
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 5/2005
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-005-1726-2

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