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Renin–angiotensin system gene polymorphisms predict the progression to renal insufficiency among Asians with lupus nephritis

Abstract

The renin–angiotensin system (RAS) is a strong candidate as a mediator for the development and progression of lupus nephritis (LN). We performed an ethnically stratified analysis of 642 systemic lupus erythematosus (SLE) patients to determine whether various functional RAS gene polymorphisms are associated with SLE renal outcomes. Patients were genotyped for two angiotensin-converting enzyme (ACE) gene polymorphisms: Alu insertion/deletion (I/D) and 23 949 (CT)2/3, and for two angiotensinogen (Atg) gene polymorphisms: M235T and C-532T. Multivariate analyses demonstrated associations between the ACE I/D, ACE (CT)2/3 and Atg C-532T functional polymorphisms and LN among Asians. In stratified analyses among LN cases according to high vs low glomerular filtration rate (GFR), associations remained significant for the ACE D (odds ratio (OR) 5.9, P=0.001) and (CT)2 (OR 6.2, P=0.001) alleles among Asian subjects with low GFR. Lastly, we found allelic dose-dependent associations between the ACE I/D (P=0.003), ACE (CT)2/3 (P=0.005) and Atg M235T (P=0.04) polymorphisms, and GFR analyzed as a continuous variable among Asians. These findings suggest a significant role for ACE and Atg gene sequence variation and severity of LN among Asians with SLE.

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Acknowledgements

This work was supported by NIH R01 AR44804, K24 AR02175, ES09911, T32 DK07219, DK 39776 and a grant from the National Kidney Foundation. This study was carried out in part in the General Clinical Research Center, Moffitt Hospital, University of California, San Francisco, with funds provided by the National Center for Research Resources, 5 M01 RR-00079, US Public Health Service.

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Correspondence to L A Criswell.

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Parsa, A., Lovett, D., Peden, E. et al. Renin–angiotensin system gene polymorphisms predict the progression to renal insufficiency among Asians with lupus nephritis. Genes Immun 6, 217–224 (2005). https://doi.org/10.1038/sj.gene.6364179

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