Parkos et al. (1988) identified a 242C-T polymorphism (rs4673) in exon 4 of the CYBA gene, leading to a his72-to-tyr (H72Y) substitution. Data on its frequency in Japanese (Inoue et al., 1998) and U.S. (Li et al., 1999) populations have been reported. Bedard et al. (2009) noted that the 242C-T SNP is also referred to as 214T-C (Y72H) based on numbering from the ATG codon.
Reactive Oxygen Species Generation
Bedard et al. (2009) analyzed 7 CYBA polymorphisms and NOX2-dependent reactive oxygen species (ROS) generation in 50 unrelated healthy Caucasian individuals. The authors identified 11 haplotypes, which could be grouped into 7 haplogroups. Only 1 haplogroup, designated 'C' and containing the 214T-C, 521T-C (rs1049254, 549C-T, V174A), and the 3-prime UTR 24G-A (rs1049255, 640A-G) SNPs, had a significant effect on ROS production, showing markedly reduced ROS generation compared to other haplotypes. Although functional analysis demonstrated significantly reduced reporter gene activity with the A allele of the 3-prime UTR SNP 24G-A compared to the G allele (p = 0.0055), haplotype analysis indicated that the observed effect on ROS production was due to the strong contribution of haplotype C. Bedard et al. (2009) suggested that inconsistencies found in published reports might be due to the analysis of individual SNPs rather than haplotypes.
