CYP3A5 polymorphism and sensitivity of blood pressure to dietary salt in Japanese men

The cytochrome P-450 3A5 (CYP3A5) gene has recently been implicated in renal sodium reabsorption and blood pressure regulation. The genetic effect of CYP3A5*1 (expressor) and *3 (reduced-expressor) variants on blood pressure has been studied in African Americans and Caucasians, but not yet in the Asian population. In this cross-sectional study, 238 Japanese male workers were examined to determine whether CYP3A5 *1*3 affects the blood pressure level, taking daily salt intake into account as a potential gene-environment interaction. The A6986G polymorphism was determined by melting curve analysis, and the salt intake level was inferred from spot urine specimen by calculating 24-h urinary sodium excretion. CYP3A5 *1*3 per se had no association with systolic blood pressure (SBP) and only a weak association was detected for diastolic blood pressure (DBP) (*1/*1 vs *3/*3, P=0.038), which was strengthened after adjustment with age and body mass index (*1/*1 vs*3/*3, P=0.007; *1/*1 vs*1/*3, P=0.045). Significant interactions between the genotype and salt intake were observed in both SBP (P=0.046) and DBP (P=0.003). SBP and DBP were significantly associated with the level of salt intake in*3/*3 (P<0.001) but not in *1 carriers. *1carrier had higher blood pressure than *3/*3, but only in those with low salt intake. These results suggest that CYP3A5 variants may be a determinant of salt sensitivity of blood pressure in Japanese men. Journal of Human Hypertension (2010) 24, 345-350; doi:10.1038/jhh.2009.74; published online 8 October 2009