CYBA Gene Polymorphisms, Lipid Parameters and Atherogenic Indices: A Cohort Study of Healthy Individuals Without Prior Lipid-Lowering Therapy

Abstract

Single-nucleotide polymorphisms (SNPs) in the CYBA gene, encoding the p22phox subunit of vascular NADPH oxidases, have been associated with atherosclerosis-related disorders. This association may partly reflect their involvement in lipid metabolism. We investigated the effects of seven CYBA SNPs (rs7195830, rs1049255, rs4673, rs13306296, rs72811418, rs16966671, and rs9932581) on systemic lipid profiles (total cholesterol, HDL-C, LDL-C, and triglycerides) and six lipid-derived atherogenic indices in 220 blood donors who had never received lipid-lowering therapy. Genotyping was performed using PCR-RFLP and TaqMan PCR. Serum lipid concentrations were determined by enzymatic colorimetric methods. For all SNPs, in silico analyses assessed allele-specific binding (ASB) of transcription factors (TFs) and gene expression in cardiovascular tissues. Statistically significant differences in lipid parameters were observed among the rs7195830, rs1049255, and rs13306296 variants. In silico analyses indicated ASB of TFs for rs1049255 and rs13306296 and genotype-dependent effects of rs13306296 and rs4673 on CYBA expression. Notably, the G allele/GG genotype of rs13306296 was associated with the least favorable lipid profile across multiple parameters, preferential binding of thirteen TFs, and increased CYBA expression in aorta and heart tissues. In conclusion, CYBA variants influence the systemic lipid profile and lipid-derived atherogenic markers in individuals untreated with lipid-lowering drugs, potentially through modulation of CYBA expression.

The authors' abstract, as published at the source. International Journal of Molecular Sciences, 2026 · DOI ↗