Resumen
Durante la última década se ha debatido la asociación entre el polimorfismo de inserción/deleción de la enzima convertidora de angiotensina (ECA) y la nefropatía diabética. Para aclarar esta situación actualizamos nuestro metanálisis previo para incluir algunos estudios pertinentes publicados desde 1994, lo que arroja un total de 17 791 sujetos provenientes de 53 estudios. Los casos (n = 9 556) eran personas con diabetes tipo 1 o tipo 2 con nefropatía diabética incipiente o avanzada, mientras que los controles (n = 8 235) eran en su mayor parte normoalbuminúricos. No se detectó ningún sesgo obvio de publicación. Con el uso de una definición de caso mínima sobre la base de la nefropatía diabética incipiente, los sujetos con genotipo II tuvieron una disminución del 22% en el riesgo de enfermedad en comparación con los portadores del alelo D (OR acumulada = 0.78, IC 95% = 0.70-0.87). Si bien se observó una disminución del riesgo entre pacientes de raza blanca con diabetes tipo 1 o tipo 2, la asociación fue más pronunciada entre los asiáticos (chinos, japoneses, coreanos) con diabetes tipo 2 (OR = 0.64, IC 95% = 0.51-0.80); este OR es significativamente diferente del obtenido para los pacientes de raza blanca con diabetes tipo 2 (OR = 0.89, IC 95% = 0.78-1.01) (p = 0.0105). Con una definición de caso más estricta, basada en la nefropatía diabética avanzada, se observó una reducción comparable del riesgo del 19% al 30% entre los tres subgrupos. Esta reducción fue estadísticamente significativa entre los asiáticos con diabetes tipo 2 y los caucásicos con diabetes tipo 1, pero no entre los de raza blanca con diabetes tipo 2. Este metanálisis actualizado fortalece la hipótesis de que la variación genética en el locus de la ECA contribuye al riesgo de la nefropatía diabética.
Palabras clave
polimorfismo ECA, nefropatía diabética, etnia, sesgo de publicación, modelo de efectos aleatorios
Clasificación en siicsalud
Artículos originales> Expertos del Mundo>
página www.siicsalud.com/des/des053/07724001.htm
Especialidades
Principal: Genética Humana
Relacionadas: Bioquímica, Cardiología, Diabetología, Medicina Interna, Nefrología y Medio Interno
Enviar correspondencia a:
Daniel Ng, Yong Loo Lin School of Medicine, National University of Singapore
Dept of Community, Occupational and Family Medicine
, 117597, Singapur, Singapur
Patrocinio y reconocimiento
Este estudio recibió el apoyo del National Medical Research Council, Singapur (NMRC/0850/2003, NMRC/1018/2005).
Artículo completo
(castellano)
Extensión:
+/- 6.35 páginas impresas en papel A4
Exclusivo para suscriptores/ assinantes |
GENETIC VARIATION AT THE ANGIOTENSIN-I CONVERTING ENZYME LOCUS AND THE RISK FOR DIABETIC NEPHROPATHY: AN UPDATE BASED ON 53 STUDIES AND 17 791 SUBJECTS
Abstract
The association between the ACE insertion/deletion polymorphism and diabetic nephropathy has been debated for the past decade. To clarify this situation, we have updated our previous meta-analysis to include relevant studies published since 1994, yielding a total of 17 791 subjects from 53 studies. Cases (n = 9 556) were type 1 or 2 diabetic subjects with incipient or advanced diabetic nephropathy while controls (n = 8 235) were largely normoalbuminuric. No obvious publication bias was detected. Using a minimal case definition based on incipient diabetic nephropathy, II subjects had a 22% lower disease risk compared to D allele carriers (pooled OR = 0.78, 95%CI = 0.70-0.87). While there was a risk reduction among Caucasians with either type 1 or type 2 diabetes, the association was most marked among type 2 diabetic Asians (Chinese, Japanese, Koreans) (OR = 0.64, 95%CI = 0.51-0.80); this OR is significantly different from that obtained for type 2 diabetic Caucasians (OR = 0.89, 95%CI = 0.78-1.01) (p = 0.0105). With a stricter case definition based on advanced diabetic nephropathy, a comparable risk reduction of 19-30% was observed among the three subgroups. This reduction was statistically significant among type 2 diabetic Asians and Caucasians with type 1 but not type 2 diabetes. This updated meta-analysis strengthens the hypothesis that genetic variation at the ACE locus contributes to risk for diabetic nephropathy.
Key words
ACE polymorphism, diabetic nephropathy, ethnicity, publication bias, random effects model
|
 |
Full text
(english)
para suscriptores/ assinantes
|
Bibliografía del artículo
1. Singapore Renal Registry. First report of the Singapore Renal Register 1997.
2. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD. U.S. Renal Data System Annual Data Report: Atlas of End-Stage Renal Disease in the United States 2004.
3. Jones CA, Krolewski AS, Rogus J, et al. Epidemic of end-stage renal disease in people with diabetes in the United States population: do we know the cause? Kidney Int 67:1684-91, 2005.
4. Ng DPK, Krolewski AS. Molecular genetic approaches for studying the etiology of diabetic nephropathy. Current Mol Med 5:511-27, 2005.
5. Ng DPK, Tai BC, Koh D, et al. Angiotensin-I converting enzyme insertion/deletion polymorphism and diabetic nephropathy: A meta-analysis of studies reported during 1994-2004 and comprising 14,727 subjects. Diabetologia 48:1008-16, 2005.
6. Arzu Ergen H, Hatemi H, Agachan B, et al. Angiotensin-I converting enzyme gene polymorphism in Turkish type 2 diabetic patients. Exp Mol Med 36:345-50, 2004.
7. Degirmenci I, Kebapci N, Basaran A, et al. Frequency of angiotensin-converting enzyme gene polymorphism in Turkish type 2 diabetic subjects. Int J Clin Pract 59:1137-42, 2005.
8. Shestakova MV, Vikulova OK, Nosikov VV. Role of genetic factors and arterial hypertension in development and progression of diabetic nephropathy (DN) in type 1 diabetes mellitus. Diabetes 54(Suppl 1):A195, 2005.
9. Canani LH, Costa LA, Crispim D, et al. The presence of allele D of angiotensin-converting enzyme polymorphism is associated with diabetic nephropathy in patients with less than 10 years duration of type 2 diabetes. Diabet Med 22:1167-72, 2005.
10. Wang Y, Ng MCY, So WY, et al. Prognostic effect of insertion/deletion polymorphism of the ACE gene on renal and cardiovascular clinical outcomes in Chinese patients with type 2 diabetes. Diabetes Care 28:348-54, 2005.
11. Ng DPK, Placha G, Choo S, et al. A disease haplotype for advanced nephropathy in type 2 diabetes at the ACE locus. Diabetes 55:2660-63, 2006.
12. Whitehead A. Meta-analysis of controlled clinical trials. Chichester: John Wiley & Sons, pp. 197-213, 2002.
13. Fleiss JL. The statistical basis of meta-analysis. Statistical Methods in Medical Research 2:121-145, 1993.
14. Armitage P, Berry G. Statistical methods in medical research, 3rd ed. London: Blackwell, pp. 521, 1994.
15. Keavney B, McKenzie CA, Connell JMC, et al. Measured haplotype analysis of the angiotensin-I converting enzyme gene. Hum Mol Genet 7:1745-51, 1998.
16. Navar LG. The intrarenal renin-angiotensin system in hypertension. Kidney Int 65:1522-32, 2004.
17. Ruster C, Wolf G. Renin-angiotensin-aldosterone system and progression of renal disease. J Am Soc Nephrol 17:2985-91, 2006.
18. Jacobsen PK, Tarnow L, Parving HH. Time to consider ACE insertion/deletion genotypes and individual renoprotective treatment in diabetic nephropathy? Kidney Int 69:1293-95, 2006. |
|
