Genetic variance of SGK-1 is associated with blood pressure, blood pressure change over time and strength of the insulin-diastolic blood pressure relationship

Abstract

Background: Insulin stimulation of the serum- and glucocorticoid-regulated kinase 1 (SGK-1) prolongs the half-life of the epithelial sodium channel, a protein which is essential for blood pressure regulation. The aim of this study was to investigate if variation in the SGK-1 gene is associated with increased blood pressure and strength of the insulin-blood pressure relationship.

Methods: A promoter C/T, an intron 6 C/T and an exon 8 C/T polymorphism in the SGK-1 gene were genotyped in 4830 subjects from the Malmö Diet and Cancer (MDC) material of whom 4001 were free from antihypertensive medication. Of these, 2171 subjects had also been investigated 11.2 +/- 4.4 years earlier in the Malmö Preventive Project (MPP).

Results: In untreated MDC subjects, intron 6 CC genotype carriers had higher diastolic blood pressure than carriers of the T allele (P = 0.02) and exon 8 C allele carriers had higher systolic blood pressure than TT genotype carriers (P = 0.05). Subjects simultaneously carrying the intron 6 CC genotype and the exon 8 CC or CT genotype (SGK-1 risk) had higher systolic blood pressure (P = 0.03) and higher diastolic blood pressure (P = 0.009) than noncarriers. From MPP to MDC, the percent change in blood pressure per year was higher for systolic blood pressure (P = 0.002) and diastolic blood pressure (P = 0.001) in SGK-1 risk carriers than noncarriers. The correlation between fasting plasma insulin concentration and diastolic blood pressure was stronger in SGK-1 risk carriers than in non-carriers (P = 0.04).

Conclusion: Our data suggest that SGK-1 risk carriers are at increased risk of hypertension and are more sensitive to the blood pressure elevating effects associated with hyperinsulinemia.