NAD (P) H oxidase p22 phox C242T polymorphism affects LDL particle size and insulin resistance in Japanese subjects.

Elevated cardiovascular risk is associated with an increased number of small, dense low-density lipoprotein (LDL) particles, which exhibit increased susceptibility to lipid oxidation, however, the mechanism determining LDL particle size has never been fully elucidated. We have examined the association between the C242T polymorphism of the p22 phox gene, which is a small subunit of vascular NAD(P)H oxidase, and both LDL particle size and clinical characteristics in 260 healthy subjects. Peak LDL particle diameter (LDL-PPD) was measured by continuous disk polyacrylamide gel electrophoresis. Twenty-one of the 217 subjects with the CC genotype showed pattern B (median LDL-PPD under 25.5 nm), whereas, none of the 43 subjects with TC + TT genotypes showed pattern B. The pattern B fraction was significantly larger in the CC group than in the TC + TT group (p = 0.030). The subjects with the CC genotype also showed a significantly higher fasting glucose level, plasma insulin level, and insulin resistance index of homeostasis model assessment (HOMA-R) than those with the TC + TT genotype. Our data demonstrate that variation in the small NAD(P)H oxidase subunit p22 phox gene substantially influences LDL particle size and may also reflect differences in the insulin sensitivity of non-diabetic subjects.