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This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: 33/3/323    most recent 00248.2007v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ji, Y. Articles by Weinshilboum, R. M. PubMed PubMed Citation Articles by Ji, Y. Articles by Weinshilboum, R. M.

Human phenylethanolamine N-methyltransferase genetic polymorphisms and exercise-induced epinephrine release

¹ Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Mayo Foundation, Rochester, Minnesota
² Department of Internal Medicine, Mayo Clinic College of Medicine, Mayo Foundation, Rochester, Minnesota
³ Department of Health Sciences Research, Mayo Clinic College of Medicine, Mayo Foundation, Rochester, Minnesota
⁴ Department of Anesthesiology, Mayo Clinic College of Medicine, Mayo Foundation, Rochester, Minnesota
⁵ Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, Ohio

Phenylethanolamine N-methyltransferase (PNMT) catalyzes the synthesis of epinephrine from norepinephrine. We previously identified and functionally characterized common sequence variation in the PNMT gene. In the present study, we set out to determine whether common PNMT genetic polymorphisms might be associated with individual variation in circulating epinephrine levels during exercise in 74 Caucasian American subjects. Circulating epinephrine levels were measured in each subject at baseline and during two different levels of exercise, 40% and 75% of peak workload. The PNMT gene was resequenced with DNA from each study subject. Eight novel PNMT polymorphisms were identified, including a C319T (Arg107Cys) nonsynonymous single nucleotide polymorphism (SNP) and I1G(280)A, a SNP located in the first intron of the gene. The I1G(280)A SNP was significantly associated with decreased exercise-induced circulating epinephrine levels and with a decreased epinephrine-to-norepinephrine ratio. The Cys107 recombinant allozyme displayed significantly lower levels of both PNMT activity and immunoreactive protein than the wild-type allozyme after transfection into COS-1 cells, but it did not appear to be associated with level of epinephrine in these subjects. Electrophoretic mobility shift and reporter gene assays performed with the I1G(280)A SNP indicated that this polymorphism could bind nuclear proteins and might modulate gene transcription. Our studies suggest that functionally significant variant sequence in the human PNMT gene might contribute to individual variation in levels of circulating epinephrine during exercise.

gene resequencing; functional genomics; exercise studies; repeated-measurements analysis; haplotypes; single nucleotide polymorphism; nonsynonymous single nucleotide polymorphism