Association of the G-463A myeloperoxidase gene polymorphism with renal disease in African Americans with systemic lupus erythematosus.
OBJECTIVE
Myeloperoxidase (MPO) is an enzyme expressed in neutrophils that is involved in tissue damage in inflammatory renal diseases. A functional G to A single-nucleotide polymorphism (SNP) is present at position -463 of the MPO promoter region and is associated with altered MPO expression. We hypothesized that the G-463A MPO SNP is a risk factor for developing lupus nephritis (LN) due to its potential influence on the inflammatory response.


METHODS
DNA from 229 patients with SLE and 277 controls from the Carolina Lupus cohort, 58 African American patients from the Sea Island Lupus Cohort, and 51 African American patients from the Lupus Multiplex Registry and Repository were genotyped by PCR. A linear regression model was used to examine relationships between the MPO genotype, case/control status, demographic characteristics, and LN.


RESULTS
There was no association of MPO genotype with systemic lupus erythematosus (SLE). However, the odds of developing LN were significantly higher among those with an A allele, compared to those without, in African American cases of all 3 cohorts. When the likelihood of developing LN was compared across MPO genotypes, the risk of developing LN was significantly higher among cases with a GA genotype versus GG (OR 2.11, 95% CI 1.12 to 3.97) and even higher with AA versus GG (OR 3.52, 95% CI 1.41 to 8.77).


CONCLUSIONS
While the G-463A MPO SNP is not a risk factor for developing SLE, the low expressing A allele is a significant risk factor for developing LN that is gene dosage-dependent in African Americans.
Bouali
Henda
H
Department of Medicine, Division of Rheumatology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Nietert
Paul
P
Nowling
Tamara M
TM
Pandey
Janardan
J
Dooley
Mary Anne
MA
Cooper
Glinda
G
Harley
John
J
Kamen
Diane L
DL
Oates
Jim
J
Gilkeson
Gary
G
D000328:Adult; D001741:Black or African American / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D007674:Kidney Diseases / Q000201:enzymology / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009195:Peroxidase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011897:Random Allocation
D009195:Peroxidase