Angiotensin-converting enzyme (insertion/deletion) and endothelial nitric oxide synthase polymorphisms in patients with systemic lupus erythematosus.
OBJECTIVE
Genetic polymorphisms in the angiotensin-converting enzyme (ACE) and endothelial nitric oxide synthase (eNOS) are linked with expression and/or progression of renal disease. We hypothesized that polymorphisms in the genes coding for ACE and eNOS may influence the development and/or progression of systemic lupus erythematosus (SLE) and lupus nephritis given their linkage with other renal diseases.


METHODS
DNA from patients with SLE (n = 227) and their age and sex matched controls (n = 275) from the Carolina Lupus (CLU) Study cohort was assessed for ACE and eNOS polymorphisms. Seventy patients had biopsy-proven lupus nephritis. Two different eNOS polymorphisms (eNOS promoter T-786(R)C nucleotide substitution and eNOS 27 base pair tandem repeat in intron 4) and the ACE insertion/deletion (I/D) polymorphism in intron 16 were examined by restriction fragment length polymorphism-polymerase chain reaction.


RESULTS
Allele frequency of the eNOS polymorphisms varied significantly between SLE patients and controls. There was no association of these polymorphisms with lupus within ethnic groups. We found no association of the polymorphism with the development of renal disease. No association was observed for the ACE I/D polymorphism with SLE or nephritis, or with ethnicity or sex.


CONCLUSIONS
eNOS genetic polymorphisms differed significantly across ethnic groups. There was no significant increased risk of SLE and/or lupus nephritis associated with eNOS or ACE polymorphisms in either the African American or Caucasian groups compared to ethnically matched controls. These studies emphasize the need to control for ethnicity when investigating genetic polymorphisms and disease.
Douglas
Glenn
G
Medical Research Service, Ralph H. Johnson Veterans Administration Medical Center and Medical University of South Carolina, Charleston, South Carolina, USA.
Reilly
Christopher
C
Dooley
Mary Anne
MA
Page
Grier
G
Cooper
Glinda
G
Gilkeson
Gary
G
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D007438:Introns; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D009657:North Carolina / Q000453:epidemiology; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013022:South Carolina / Q000453:epidemiology
C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A