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.

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Numerous linkage studies have indicated chromosome 18q21-22 as a locus of importance for blood pressure regulation. This locus harbors the neural precursor cell expressed developmentally downregulated 4-like (NEDD4L) gene, which is instrumental for the regulation of the amiloride-sensitive epithelial sodium channel (ENaC). In a linkage study of 16 markers (including two single nucleotide polymorphism markers located within the NEDD4L gene) on chromosome 18 between 70-104 cM and ambulatory blood pressure (ABP), in 118 families, the strongest evidence of linkage was found for 24 h and day-time systolic ABP at the NEDD4L locus (82.25 cM) (P=0.0014). In a large population sample (n=4001), we subsequently showed that a NEDD4L gene variant (rs4149601), which by alternative splicing leads to varying expression of a functionally crucial C2 domain, was associated with diastolic blood pressure (DBP) (P=0.03) and DBP progression over time (P=0.04). A genotype combination of the rs4149601 and an intronic NEDD4L marker (rs2288774) was associated with systolic blood pressure (SBP) (P=0.01), DBP (P=0.04), and progression of both SBP (P=0.03) and DBP (P=0.05) over time. A quantitative transmission disequilibrium test in the family material of the rs4149601 supported this NEDD4L variant as being at least partially causative of the linkage result. In conclusion, our findings suggest that the chromosome 18 linkage peak at 82.25 cM is explained by genetic NEDD4L variation affecting cross-sectional and longitudinal blood pressure, possibly as a consequence of altered NEDD4L interaction with ENaC.

Aims/hypothesis. To study the risk of women with impaired fasting glucose (IFG) as against impaired glucose tolerance (IGT) developing diabetes. Methods. Oral glucose tolerance tests (75 g) were done in 265 women selected at random at baseline (age 55±57 years) and at a 10-year follow-up. Of the women 42 had IFG/NGT (fasting glucose 6.1±6.9 mmol/l, 2-h glucose < 7.8 mmol/l), 66 IGT/ NFG (2-h glucose 7.8±11.0 mmol/l, fasting glucose < 6.1 mmol/l), 30 IGT/IFG and 127 NFG/NGT. Results. The 10-year progression to diabetes was similar in IGT/NFG (12.1 %) and IFG/NGT groups (11.9 %, p = 0.97). In IGT/IFG, 20.0 % had developed diabetes, which was not significantly higher than in IFG/NGT and IGT/NFG (p = 0.53). In NFG/ NGT at baseline, only 3.9 % had developed diabetes, which was lower than in the other groups (p = 0.023). Conclusion/interpretation. Fasting and 2-h glucose concentrations are equally good in predicting diabetes development over a 10-year period in Caucasian postmenopausal women. Because IGT is more common than IFG, measuring only fasting glucose concentrations would, however, result in missing a prediabetic stage in a large group of people at risk for diabetes and cardiovascular diseases. [Diabetologia (2000