Nitric oxide synthase 2 promoter polymorphisms and systemic lupus erythematosus in african-americans.
OBJECTIVE
Systemic lupus erythematosus (SLE) is an autoimmune disease in which morbidity and mortality are higher in African-Americans. The etiology of this racial disparity is unknown. A genetic predisposition to enhanced nitric oxide (NO) production may predispose African-Americans to develop SLE and may increase disease severity. We have demonstrated a correlation between NO production and disease activity in SLE. Two polymorphisms in the inducible NO synthase (NOS2) promoter region (G-954C and CCTTT microsatellite repeat polymorphisms) are associated with improved outcome in some African patients with malaria. This study was designed to determine if these polymorphisms are associated with SLE.


METHODS
We assessed the frequency of both the G-954C and CCTTT microsatellite repeat NOS2 promoter polymorphisms in a cohort of patients with SLE and age, sex, and race matched controls in North Carolina and South Carolina.


RESULTS
Both polymorphisms were more frequent among African-American female SLE patients when compared with controls (p = 0.04 for the G-954C polymorphism and p = 0.03 for the CCTTT-8 repeat polymorphism). Further, the G-954C and CCTTT-8 repeat polymorphisms were in linkage disequilibrium (D cent = 0.89, p = 0.0001) among African-American female SLE patients.


CONCLUSIONS
Altered genetic control of NOS2 transcription may be a risk factor for SLE among African-American females. The extent of linkage disequilibrium between the G-954C and CCTTT-8 repeat NOS2 promoter polymorphisms suggests that they were co-inherited.
Oates
Jim C
JC
Department of Medicine, Ralph H. Johnson VA Medical Center (VAMC) and Medical University of South Carolina, Charleston 29425, USA. oatesjc@musc.edu
Levesque
Marc C
MC
Hobbs
Maurine R
MR
Smith
Erica Grace
EG
Molano
Ivan D
ID
Page
Grier P
GP
Hill
Bruce S
BS
Weinberg
J Brice
JB
Cooper
Glinda S
GS
Gilkeson
Gary S
GS
D000483:Alleles; D044383:Black People / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012307:Risk Factors; D017678:Sex Distribution; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000097:blood; D044465:White People / Q000235:genetics; D001741:Black or African American
C002744:3-nitrotyrosine; D014443:Tyrosine; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II