A genome-wide scan in Dutch families with familial combined hyperlipidemia revealed significant linkage of systolic blood pressure to a locus on chromosome 4p (lod score 4.6 after adjustment).
Observational
A genome-wide scan in Dutch families with familial combined hyperlipidemia identified a significant linkage locus for systolic blood pressure on chromosome 4p.
Effect estimate: LOD 4.6
Genes contributing to common forms of hypertension are largely unknown. A number of studies in humans and in animal models have revealed associations between insulin resistance, dyslipidemia, and elevated hypertension. To identify genes contributing to blood pressure (BP) variation associated with insulin-resistant dyslipidemia, we conducted a genome-wide scan for BP in a set of 18 Dutch families exhibiting the common lipid disorder familial combined hyperlipidemia. Our results reveal a locus on chromosome 4 that exhibits 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 adjustment 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 chromosome 4 locus contains an attractive candidate gene, alpha-adducin, which has been associated with altered BP in animal studies and in some human populations. However, we found no evidence for an association between 2 intragenic 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 previously observed in a separate insulin-resistant population. In addition, we also obtained suggestive evidence for linkage of systolic BP (lod=2.4) and plasma apolipoprotein B levels (lod=2.0) to a locus on proximal chromosome 19p. In conclusion, our genome scan results support the existence of multiple genetic factors that can influence both BP and plasma lipid parameters.
Allayee et al. (Mon,) conducted a observational in Familial combined hyperlipidemia and blood pressure variation. Genome-wide scan was evaluated on Linkage to systolic blood pressure (LOD 4.6). A genome-wide scan in Dutch families with familial combined hyperlipidemia revealed significant linkage of systolic blood pressure to a locus on chromosome 4p (lod score 4.6 after adjustment).