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

A. Parsa, D. H. Lovett, E. A. Peden, Lingxiang Zhu, Michael F Seldin, L. A. Criswell

Research output: Contribution to journalArticle

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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 23949 (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.

Original languageEnglish (US)
Pages (from-to)217-224
Number of pages8
JournalGenes and Immunity
Volume6
Issue number3
DOIs
StatePublished - May 2005

Fingerprint

Lupus Nephritis
Peptidyl-Dipeptidase A
Renin-Angiotensin System
Angiotensinogen
Renal Insufficiency
Glomerular Filtration Rate
Systemic Lupus Erythematosus
Genes
Odds Ratio
Multivariate Analysis
Alleles
Kidney

Keywords

  • Angiotensin-converting enzyme
  • Angiotensinogen
  • Genetics
  • Lupus nephritis
  • Polymorphisms
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

Renin-angiotensin system gene polymorphisms predict the progression to renal insufficiency among Asians with lupus nephritis. / Parsa, A.; Lovett, D. H.; Peden, E. A.; Zhu, Lingxiang; Seldin, Michael F; Criswell, L. A.

In: Genes and Immunity, Vol. 6, No. 3, 05.2005, p. 217-224.

Research output: Contribution to journalArticle

Parsa, A. ; Lovett, D. H. ; Peden, E. A. ; Zhu, Lingxiang ; Seldin, Michael F ; Criswell, L. A. / Renin-angiotensin system gene polymorphisms predict the progression to renal insufficiency among Asians with lupus nephritis. In: Genes and Immunity. 2005 ; Vol. 6, No. 3. pp. 217-224.
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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 23949 (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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