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. CONCLUSION: 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.
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 SLEpatients 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 SLEpatients. CONCLUSION: 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.
Authors: Henda Bouali; Paul Nietert; Tamara M Nowling; Janardan Pandey; Mary Anne Dooley; Glinda Cooper; John Harley; Diane L Kamen; Jim Oates; Gary Gilkeson Journal: J Rheumatol Date: 2007-09-15 Impact factor: 4.666
Authors: Cecilia M Johansson; Renata Zunec; Mercedes A García; Hugo R Scherbarth; Guillermo A Tate; Sergio Paira; Sandra M Navarro; Carlos E Perandones; Susana Gamron; Alejandro Alvarellos; Cesar E Graf; Jorge Manni; Guillermo A Berbotto; Simon A Palatnik; Luis J Catoggio; Cristina G Battagliotti; Gian Domenico Sebastiani; Sergio Migliaresi; Mauro Galeazzi; Bernardo A Pons-Estel; Marta E Alarcón-Riquelme Journal: Hum Genet Date: 2004-07-01 Impact factor: 4.132
Authors: Marc C Levesque; Maurine R Hobbs; Charles W O'Loughlin; Jennifer A Chancellor; Youwei Chen; Ariana N Tkachuk; Jennifer Booth; Kistie B Patch; Sallie Allgood; Ann R Pole; Carolyn A Fernandez; Esther D Mwaikambo; Theonest K Mutabingwa; Michal Fried; Bess Sorensen; Patrick E Duffy; Donald L Granger; Nicholas M Anstey; J Brice Weinberg Journal: Hum Genet Date: 2009-10-27 Impact factor: 4.132
Authors: Ruchi Shah; Cynthia Amador; Kati Tormanen; Sean Ghiam; Mehrnoosh Saghizadeh; Vaithi Arumugaswami; Ashok Kumar; Andrei A Kramerov; Alexander V Ljubimov Journal: Exp Eye Res Date: 2021-01-21 Impact factor: 3.467