RESUMO
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.
Assuntos
Pressão Sanguínea/genética , Cromossomos Humanos Par 4/genética , Predisposição Genética para Doença/genética , Genoma Humano , Hiperlipidemias/genética , Adulto , Pressão Sanguínea/fisiologia , Proteínas de Ligação a Calmodulina/genética , Mapeamento Cromossômico , Cromossomos Humanos Par 19/genética , Cromossomos Humanos Par 6/genética , Cromossomos Humanos Par 8/genética , Diástole , Saúde da Família , Feminino , Ligação Genética , Humanos , Hiperlipidemias/fisiopatologia , Escore Lod , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade , Países Baixos , SístoleRESUMO
Familial combined hyperlipidemia (FCHL) is a complex genetic disorder of unknown etiology. Recently, 'modifier' genes of the FCHL phenotype, such as the apolipoprotein AI-CIII-AIV gene cluster and LPL, have been identified in several populations. A 'major' gene for FCHL has been identified in a Finnish isolate which maps to a region syntenic to murine chromosome 3 where a locus for combined hyperlipidemia has been identified. We review these and other recent studies which indicate that FCHL is genetically heterogeneous.
