Abstract-Essential hypertension remains a major risk factor for cardiovascular and cerebrovascular diseases. As a complex multifactorial disease, elucidation of susceptibility loci remains elusive. ATP1A1 and Dear are candidate genes for 2 closely linked rat chromosome-2 blood pressure quantitative trait loci. Key Words: ␣ 1 Na,K-ATPase Ⅲ Dear Ⅲ hypertension Ⅲ genetics Ⅲ risk factor E ssential hypertension is a major public health concern because of its high prevalence and its role as a leading risk factor for leading causes of death and morbidity in the developed world 1 : coronary artery disease, stroke, chronic renal disease, and peripheral vascular disease. As a multifactorial disorder in which the onset and severity of the condition are influenced by both genetic and environmental factors, 2 elucidation of underlying genetic mechanisms of hypertension is critical but remains elusive because of the polygenic nature and the complexity that is brought on by environmental and the intrinsic genetic heterogeneity of human populations. 2 For complex multifactorial diseases with clinical heterogeneity, such as hypertension, genetic studies of inbred rat models of polygenic (essential) hypertension are instrumental in identifying blood pressure quantitative trait loci (BP-QTLs) and candidate susceptibility genes for subsequent testing in human essential hypertension.We have recently detected 2 closely linked, sex-specific BP-QTLs on chromosome-2 (chr2) affecting salt-sensitive hypertension in a total genome scan of (Dahl salt-sensitive [S]ϫDahl salt-resistant [R]]F2 intercross male and female rat hybrids, respectively. 3 These 2 chr2 BP-QTLs correspond to 2 candidate genes supported by cumulative experimental evidence. Briefly, molecular genetic 4 -6 and transgenic 7 analyses demonstrate that a functionally significant Q276L variant of the ␣ 1 N,K-ATPase (ATP1A1), which exhibits abnormal K transport 4,5

Our results confirm the difficulty in dissecting both essential hypertension and pharmacogenomics when analyzing the effect of single genes in complex multifactorial traits.

Our study confirmed the sex-specific association of GNB3 with the blood pressure response to atenolol with no substantial advantage of the analysis of haplotypes over SNPs.

Using a genome-wide approach, we identified the CAMK1D gene as a novel locus associated with blood pressure response to losartan. CAMK1D gene characterization may represent a useful tool to personalize the treatment of essential hypertension.