Published Online
on October 7, 2002

A more recent version of this article appeared on November 1, 2002

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Submitted on June 18, 2002
Revised on July 20, 2002

Genomic Association/Linkage of Sodium Lithium Countertransport in CEPH Pedigrees

Nicholas J. Schork; Jeffrey P. Gardner; Li Zhang; Danielle Fallin; Bonnie Thiel; Hieronim Jakubowski; and Abraham Aviv^*

From the Department of Epidemiology and Biostatistics, Case Western Reserve University (N.J.S., D.F., B.T.), Cleveland, Ohio; The Program for Population Genetics and Department of Biostatistics, Harvard University School of Public Health (N.J.S.), Boston, Mass; The Jackson Laboratory (N.J.S.), Bar Harbor, Maine; and Hypertension Research Center (J.P.G., L.Z., A.A.) and Department of Microbiology and Molecular Genetics (H.J.), University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark. Dr Fallin is now at the Department of Epidemiology, Johns Hopkins University, Baltimore, Md. Dr Schork is now at the Department of Psychiatry, University of California at San Diego.

^* To whom correspondence should be addressed. E-mail: avivab{at}umdnj.edu.

Abstract—Little is known about genetic determinants explaining variation in the erythrocyte sodium-lithium countertransport (SLC), an intermediate phenotype of essential hypertension. We characterized the SLC in immortalized lymphoblasts and showed that its behavior is similar to that of erythrocyte SLC. We then performed association and linkage analyses of the SLC in immortalized lymphoblasts from 5 large pedigrees from the Center d'Etude du Polymorphisme Humain (CEPH) genomics repository. The results of these analyses showed that a number of genomic regions harboring genes involved in glutathione metabolism might explain variations in SLC activity. These findings support evidence that thiol groups play a central role in SLC activity.

Key words: oxidative stress • ion transport • lymphocytes • glutathione • intermediate phenotype

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