Genome scan for blood pressure in Dutch dyslipidemic families reveals linkage to a locus on chromosome 4p

Genes contributing to common forms of hypertension are largely unknown. A n umber of studies in humans and in animal models have revealed associations between insulin resistance, dyslipidemia, and elevated hypertension. To ide ntify genes contributing to blood pressure (BP) variation associated with i nsulin-resistant dyslipidemia, we conducted a genome-wide scan for BP in a set of 18 Dutch families exhibiting the common lipid disorder familial comb ined hyperlipidemia. Our results reveal a locus on chromosome 4 that exhibi ts a significant lod score of 3.9 with systolic BP. In addition, this locus also appears to influence plasma free fatty acid levels (lod=2.4). After a djustment for age and gender, the lod score for systolic BP increased to 4. 6, whereas the lod score for free fatty acid levels did not change. The chr omosome 4 locus contains an attractive candidate gene, alpha -adducin, whic h has been associated with altered BP in animal studies and in some human p opulations. However, we found no evidence for an association between 2 intr agenic alpha -adducin polymorphisms and systolic BP in this sample. We also observed suggestive evidence for linkage (lod=1.8) of diastolic BP to the lipoprotein lipase gene locus on chromosome 8p, supporting a finding previo usly observed in a separate insulin-resistant population. In addition, we a lso obtained suggestive evidence for linkage of systolic BP (lod=2.4) and p lasma apolipoprotein B levels (lod=2.0) to a locus on proximal chromosome 1 9p. In conclusion, our genome scan results support the existence of multipl e genetic factors that can influence both BP and plasma lipid parameters.