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Abstract-A region on human chromosome 5 (5q31.1-qter) contains several genes that encode important blood pressure regulators and thus is a good candidate for analysis of linkage and association with hypertension. We recruited 638 individuals from 212 Polish pedigrees with clustering of essential hypertension. These subjects were genotyped for 11 microsatellite markers that span this region to test for linkage to essential hypertension and systolic and diastolic blood pressures. The segment of this region of Ϸ7 cM delineated by D5S1480 and D5S500 markers was linked to blood pressures in multipoint analysis. In 2-point analysis, D5S1480 -the marker in close proximity to ␤ 2 -adrenergic receptor gene-reached the maximal linkage to essential hypertension and adjusted systolic and diastolic blood pressures, implicating this gene as a positional candidate for further association studies. Arg16Gly, Gln27Glu, and Thr164Ile-3 functional single nucleotide polymorphisms within the ␤ 2 -adrenergic receptor gene-were tested for association with essential hypertension. None of these polymorphisms showed a significant association with essential hypertension, separately or in the haplotype analysis. This study provided evidence of linkage of 5q31.1-5qter region to essential hypertension in the European population. Moreover, it implicated the chromosomal segment in close proximity to D5S1480 and D5S500. The detailed analysis of 3 single nucleotide polymorphisms does not support the role of the Key Words: chromosomes Ⅲ adrenergic receptors Ⅲ genes Ⅲ linkage Ⅲ blood pressure E ssential hypertension is a multifactorial complex trait with a strong hereditary component. Apart from genomewide scans and candidate gene approach (principal methods used in pursuit of genetic loci that may determine predisposition to essential hypertension), 1 a target chromosomal region approach combining the rationale of 2 major strategies has been postulated. 2 Selection of a small chromosomal region implicated by genome-wide searches and containing several candidate genes pathophysiologically related to the investigated phenotypes allows for denser saturation with microsatellite markers and may be followed by subsequent positional analysis. The distal segment of the long arm of chromosome 5 (5q31.1-qter) is an outstanding target chromosomal region for studies on essential hypertension, having been linked to both systolic 3 and postexercise diastolic blood pressure 4 in genome-wide scans performed in white populations. Furthermore, this region contains a cluster of genes coding for proteins known as important blood pressure regulators (␤ 2 -adrenergic receptor gene [ADRB2], ␣ 1B -adrenergic receptor, dopamine D 1 receptor, annexin VI) and implicated as possible contributors to the pathogenesis of several cardiovascular disorders (platelet-derived growth factor receptor, glutathione peroxidase).We performed a linkage analysis of this region using 3 related phenotypes: a diagnosis of essential hypertension (a qualitative trait) and 2 quantitative phenotyp...