Hak Soo Kim1, Sang-Cheol Bae, Tae-Ho Kim, Shin-Yoon Kim. 1. Department of Orthopaedic Surgery, Graduate School of Medicine, Kyungpook National University, 130 Dongdeok-ro, Jung-gu, Daegu, 700-721, Korea.
Abstract
PURPOSE: Nitric oxide (NO), a short-lived gaseous free radical, is a potent mediator of biological responses involved in the pathogenesis of autoimmune rheumatic diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Nitric oxide also serves as an important signal in physiological processes, including angiogenesis, thrombosis, and bone turnover, which are known to be related to the pathogenesis of osteonecrosis. We investigated whether NOS3 gene polymorphisms are associated with risk of osteonecrosis of the femoral head (ONFH). METHODS: Five polymorphisms in the NOS3 gene were genotyped using TaqMan assays in 306 controls, 150 SLE patients, and 50 SLE patients with ONFH (SLE_ONFH). RESULTS: We found that Asp258Asp and Glu298Asp (G894T) polymorphisms in the NOS3 gene were significantly associated with risk of ONFH. Additionally, we calculated haplotype frequencies of a linkage disequilibrium (LD) block in NOS3 (rs1799983 - rs1800780) and tested for haplotype associations. The haplotypes G-A and T-A showed significant protective (P = 1.6 × 10(-3); OR 0.39, 95 % confidence intervals (CI) 0.22-0.7) and increased risk (P = 2.0 x 10(-5)-6.0 x 10(-4); OR 3.17-3.73) effects for ONFH, respectively. CONCLUSIONS: These results suggest that exonic NOS3 polymorphisms may increase the risk of ONFH in Korean SLE patients.
PURPOSE:Nitric oxide (NO), a short-lived gaseous free radical, is a potent mediator of biological responses involved in the pathogenesis of autoimmune rheumatic diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Nitric oxide also serves as an important signal in physiological processes, including angiogenesis, thrombosis, and bone turnover, which are known to be related to the pathogenesis of osteonecrosis. We investigated whether NOS3 gene polymorphisms are associated with risk of osteonecrosis of the femoral head (ONFH). METHODS: Five polymorphisms in the NOS3 gene were genotyped using TaqMan assays in 306 controls, 150 SLEpatients, and 50 SLEpatients with ONFH (SLE_ONFH). RESULTS: We found that Asp258Asp and Glu298Asp (G894T) polymorphisms in the NOS3 gene were significantly associated with risk of ONFH. Additionally, we calculated haplotype frequencies of a linkage disequilibrium (LD) block in NOS3 (rs1799983 - rs1800780) and tested for haplotype associations. The haplotypes G-A and T-A showed significant protective (P = 1.6 × 10(-3); OR 0.39, 95 % confidence intervals (CI) 0.22-0.7) and increased risk (P = 2.0 x 10(-5)-6.0 x 10(-4); OR 3.17-3.73) effects for ONFH, respectively. CONCLUSIONS: These results suggest that exonic NOS3 polymorphisms may increase the risk of ONFH in Korean SLEpatients.
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