BACKGROUND: Previous study showed that polymorphism of the NAD(P)H oxidase p22(phox) gene is associated with atherosclerosis, although others could not confirm such association. We investigated the association between p22(phox) C242T polymorphism and thrombotic cerebral infarction and the role of this polymorphism on superoxide-production activity in human neutrophils and promyelocytic HL-60 cells as a model system. METHODS: PCR-RFLP analysis revealed that genotype and allele frequencies of C242T polymorphism in 120 patients with thrombotic cerebral infarction and 177 control subjects. The superoxide-production activity in neutrophils was determined by cytochrome c reduction assay. To clarify the role of p22(phox) C242T polymorphism on NAD(P)H oxidase activity, we used transgenic HL-60 cells transfected with expression plasmids carrying p22(phox) cDNAs with or without C242T polymorphism. RESULTS: Genotype and allele frequencies of C242T polymorphism in patients and control subjects were not significantly different. The superoxide-production activity in neutrophils with T allele was higher than in neutrophils without T allele. Moreover, expression analysis showed that superoxide-production activity in p22(phox) C242T-expressing HL-60 cells were significantly higher than in p22(phox)-expressing HL-60 cells. CONCLUSIONS: We conclude that C242T of p22(phox) gene is not involved in thrombotic cerebral infarction but more likely in increased NAD(P)H oxidase activity in phagocytes.
BACKGROUND: Previous study showed that polymorphism of the NAD(P)H oxidase p22(phox) gene is associated with atherosclerosis, although others could not confirm such association. We investigated the association between p22(phox) C242T polymorphism and thrombotic cerebral infarction and the role of this polymorphism on superoxide-production activity in human neutrophils and promyelocytic HL-60 cells as a model system. METHODS: PCR-RFLP analysis revealed that genotype and allele frequencies of C242T polymorphism in 120 patients with thrombotic cerebral infarction and 177 control subjects. The superoxide-production activity in neutrophils was determined by cytochrome c reduction assay. To clarify the role of p22(phox) C242T polymorphism on NAD(P)H oxidase activity, we used transgenic HL-60 cells transfected with expression plasmids carrying p22(phox) cDNAs with or without C242T polymorphism. RESULTS: Genotype and allele frequencies of C242T polymorphism in patients and control subjects were not significantly different. The superoxide-production activity in neutrophils with T allele was higher than in neutrophils without T allele. Moreover, expression analysis showed that superoxide-production activity in p22(phox) C242T-expressing HL-60 cells were significantly higher than in p22(phox)-expressing HL-60 cells. CONCLUSIONS: We conclude that C242T of p22(phox) gene is not involved in thrombotic cerebral infarction but more likely in increased NAD(P)H oxidase activity in phagocytes.
Authors: J E Megías-Vericat; P Montesinos; M J Herrero; F Moscardó; V Bosó; L Rojas; D Martínez-Cuadrón; R Rodríguez-Veiga; L Sendra; J Cervera; J L Poveda; M Á Sanz; S F Aliño Journal: Pharmacogenomics J Date: 2017-05-09 Impact factor: 3.550
Authors: Qing Lan; Tongzhang Zheng; Min Shen; Yawei Zhang; Sophia S Wang; Shelia H Zahm; Theodore R Holford; Brian Leaderer; Peter Boyle; Stephen Chanock Journal: Hum Genet Date: 2006-12-06 Impact factor: 4.132
Authors: X L Zhu; W J Li; X E Wang; W L Song; L Xu; L Zhang; X H Feng; R F Lu; D Shi; H X Meng Journal: Beijing Da Xue Xue Bao Yi Xue Ban Date: 2022-02-18
Authors: Roberto Schreiber; Maria C Ferreira-Sae; Juliana A Ronchi; José A Pio-Magalhães; José A Cipolli; José R Matos-Souza; José G Mill; Aníbal E Vercesi; José E Krieger; Kleber G Franchini; Alexandre C Pereira; Wilson Nadruz Junior Journal: BMC Med Genet Date: 2011-08-31 Impact factor: 2.103
Authors: Roberto Schreiber; Vera Regina Bellinazzi; Andrei C Sposito; José G Mill; José E Krieger; Alexandre C Pereira; Wilson Nadruz Journal: PLoS One Date: 2013-12-05 Impact factor: 3.240