This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brzustowicz, L. M. Articles by Aviv, A. Search for Related Content PubMed PubMed Citation Articles by Brzustowicz, L. M. Articles by Aviv, A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CALCIUM COMPOUNDS CALCIUM, ELEMENTAL Medline Plus Health Information High Blood Pressure

(Hypertension. 1997;29:158.)
© 1997 American Heart Association, Inc.

Scientific Contributions

Linkage Analysis Using Platelet-Activating Factor Ca²⁺ Response in Transformed Lymphoblasts

Linda M. Brzustowicz; Jeffrey P. Gardner; Laszlo Hopp; Elisabeth Jeanclos; Jurg Ott; Xiao Yan Yang; Zoltan Fekete; Abraham Aviv

From the Hypertension Research Program of the University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark (J.P.G., L.H., E.J., X.Y.Y., Z.F., A.A.); the Center for Molecular and Behavioral Neurosciences, Rutgers University, Newark, NJ, and the Department of Psychiatry, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark (L.M.B.); and the Statistical Genetics Laboratory, The Rockefeller University, New York, NY (J.O.).

Reprint requests to Dr Abraham Aviv, Hypertension Research Program, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, MSB-F464, 185 S Orange Ave, Newark, NJ 07103-2714

Epstein-Barr virus-transformed lymphoblasts from patients with essential hypertension demonstrate enhanced G protein-mediated cytosolic free calcium ([Ca²⁺]_i) response to platelet-activating factor (PAF). To map genes responsible for variation in G protein-coupled signaling, we used this cellular phenotype for a linkage study of transformed cell lines from the Centre d’Etude du Polymorphisme Humain (CEPH) reference pedigrees. The PAF-evoked change in [Ca²⁺]_i ranged from 20 to 392 mmol/L and was highly reproducible within each cell line. PAF-elicited [Ca²⁺]_i responses were obtained in lymphoblastic cell lines from five densely mapped pedigrees of the CEPH collection. Using PAF-evoked [Ca²⁺]_i responses as a quantitative trait, two-point sibpair linkage analyses were conducted using 5150 markers from the Collaborative Human Linkage Center (CHLC) database. Nine loci, located on chromosomes 1, 4, 10, 11, 13, 16, and 17, were suggestive of linkage, with values of P<7.4x10^-4. Multipoint linkage analysis produced a significant linkage finding (P=2.1x10^-5) in one family at D16S151, with suggestive linkage results for seven additional markers spanning a 40-cM interval of chromosome 16. Multipoint analysis produced suggestive findings of linkage to eight loci from two distinct regions of chromosome 11 in another family. These results indicate that loci involved in the control of G protein-mediated mechanisms, suggested to be involved in the pathophysiology of essential hypertension, can be identified using cell lines from general pedigrees selected without any knowledge of the blood pressure status of the donors. This strategy represents an approach to rapidly and inexpensively mapping loci related to common, complex disorders, using phenotypes that are stable in immortalized lymphoblasts together with existing reference pedigree cell lines and genotype databases.

Key Words: platelet-activating factor • cytosolic calcium • G protein

Abbreviations: CEPH = Centre d’Etude du Polymorphisme Humain • CHLC = Collaborative Human Linkage Center • cM = centimorgan • cytosolic free Ca²⁺ = [Ca²⁺]_i • EBV = Epstein-Barr virus • G protein = guanine nucleotide-binding regulatory protein • HBS = HEPES-buffered solution • NHE-1 = Na⁺/H⁺ exchanger • PAF = platelet-activating factor • Vmax = maximal reaction velocity

This article has been cited by other articles:

				T. A. Greenwood, P. E. Cadman, M. Stridsberg, S. Nguyen, L. Taupenot, N. J. Schork, and D. T. O'Connor Genome-wide linkage analysis of chromogranin B expression in the CEPH pedigrees: implications for exocytotic sympathochromaffin secretion in humans Physiol Genomics, June 17, 2004; 18(1): 119 - 127. [Abstract] [Full Text] [PDF]

				K. Itagaki, K. B. Kannan, B. B. Singh, and C. J. Hauser Cytoskeletal Reorganization Internalizes Multiple Transient Receptor Potential Channels and Blocks Calcium Entry into Human Neutrophils J. Immunol., January 1, 2004; 172(1): 601 - 607. [Abstract] [Full Text] [PDF]

				K. Fukunaga, S. Ishii, K. Asano, T. Yokomizo, T. Shiomi, T. Shimizu, and K. Yamaguchi Single Nucleotide Polymorphism of Human Platelet-activating Factor Receptor Impairs G-protein Activation J. Biol. Chem., November 9, 2001; 276(46): 43025 - 43030. [Abstract] [Full Text] [PDF]

				J. P Gardner and L. Zhang Glucocorticoid modulation of Ca2+ homeostasis in human B lymphoblasts J. Physiol., January 15, 1999; 514(2): 385 - 396. [Abstract] [Full Text] [PDF]