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(Hypertension. 2006;48:105.)
© 2006 American Heart Association, Inc.

Original Articles

Increased Support for Linkage of a Novel Locus on Chromosome 5q13 for Essential Hypertension in the British Genetics of Hypertension Study

Patricia B. Munroe; Chris Wallace; Ming-Zhan Xue; Ana Carolina B. Marçano; Richard J. Dobson; Abiodun K. Onipinla; Beverley Burke; Johannie Gungadoo; Stephen J. Newhouse; Janine Pembroke; Morris Brown; Anna F. Dominiczak; Nilesh J. Samani; Mark Lathrop; John Connell; John Webster; David Clayton; Martin Farrall; Charles A. Mein; Mark Caulfield for the Medical Research Council British Genetics of Hypertension Study

From the Clinical Pharmacology and Barts and the London Genome Centre (P.B.M., C.W., M-Z.X., A.C.M., R.J.D., A.K.P., B.B., J.G., S.J.N., J.P., C.A.M., M.C.), William Harvey Research Institute Barts and the London School of Medicine, Charterhouse Square, London, United Kingdom; Clinical Pharmacology and the Cambridge Institute of Medical Research (M.B., D.C.), University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom; BHF Glasgow Cardiovascular Research Centre, Division of Cardiovascular and Medical Sciences (A.F.D., J.C.), Department of Cardiovascular Medicine, University of Glasgow, Western Infirmary, Glasgow, United Kingdom; Department of Cardiovascular Sciences (N.J.S.), University of Leicester, Glenfield Hospital, Leicester, United Kingdom; Centre National de Genotype (M.L.), Evry, France; Medicine and Therapeutics (J.W.), Aberdeen Royal Infirmary, Aberdeen, United Kingdom; University of Oxford (M.F.), Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.

Correspondence to Mark Caulfield, Centre for Clinical Pharmacology, William Harvey Research Institute, Barts and The London, Queen Mary’s School of Medicine and Dentistry, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ UK. E-mail m.j.caulfield{at}qmul.ac.uk

Human hypertension arises from a combination of genetic factors and lifestyle influences. With cardiovascular disease set to become the number 1 cause of death worldwide, it is important to understand the etiologic mechanisms for hypertension, because these might provide new routes to improved treatment. The British Genetics of Hypertension Study has recently published a primary genome screen that identified 4 chromosomal regions of interest. We have now genotyped additional markers to confirm the most promising regions for follow-up studies. Thirty-four additional microsatellites were genotyped in our severely hypertensive affected sibling pair resource (now 1635 families with 2142 affected sibling pairs), leading to a substantial increase in information content in the regions of interest. We found increased support for linkage of chromosome 5q13 to human hypertension (multipoint logarithm of odds=2.50) with 3 adjacent markers yielding single point logarithm of odds scores of 3.22, 2.84, and 2.51. The placement of additional markers on 2q, 6q, and 9q diminished support for linkage in these regions. However, the addition of new data and families identified novel regions of interest on chromosomes 1q and 11q. The 3 positive markers in the chromosome 5 region were also genotyped in 712 distinct parent–offspring trios with the same severe phenotype to replicate linkage and association. Borderline support for replication was found (P=0.07). We found increased evidence for linkage and borderline-significant evidence for association for a hypertension susceptibility locus on chromosome 5q13 that is worthy of detailed fine mapping and assessment of candidate genes.

Key Words: genetics • hypertension, essential • polymorphism

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