Functional allelic heterogeneity and pleiotropy of a repeat polymorphism in tyrosine hydroxylase: prediction of catecholamines and response to stress in twins

Physiological Genomics
Lian ZhangDaniel T O'Connor

Abstract

Tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, has a common tetranucleotide repeat polymorphism, (TCAT)(n). We asked whether variation at (TCAT)(n) may influence the autonomic nervous system and its response to environmental stress. To understand the role of heredity in such traits, we turned to a human twin study design. Both biochemical and physiological autonomic traits displayed substantial heritability (h(2)), up to h(2) = 56.8 +/- 7.5% (P < 0.0001) for norepinephrine secretion, and h(2) = 61 +/- 6% (P < 0.001) for heart rate. Common (TCAT)(n) alleles, particularly (TCAT)(6) and (TCAT)(10i), predicted such traits (including catecholamine secretion, as well as basal and poststress heart rate) in allele copy number dose-dependent fashion, although in directionally opposite ways, indicating functional allelic heterogeneity. (TCAT)(n) diploid genotypes (e.g., [TCAT](6)/[TCAT](10i)) predicted the same physiological traits but with increased explanatory power for trait variation (in contrast to allele copy number). Multivariate ANOVA documented genetic pleiotropy: joint effects of the (TCAT)(10i) allele on both biochemical (norepinephrine) and physiological (heart rate) traits. (TCAT)(6) allele fre...Continue Reading

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References

Oct 1, 1977·American Journal of Epidemiology·M FeinleibJ O Wagner
Apr 1, 1990·Circulation·R J ParmerD T O'Connor
Jan 1, 1990·Life Sciences·B Kennedy, M G Ziegler
Jul 1, 1995·Hypertension·M A TakiyyuddinF A Wright
Sep 13, 1996·Science·N Risch, K Merikangas
May 16, 1998·Genome Research·D GordonP Green
May 23, 1998·American Journal of Human Genetics·L Almasy, J Blangero
Feb 26, 2000·Acta Physiologica Scandinavica·T Flatmark
Jun 23, 2000·Life Sciences·J L González-TrápagaM G Ziegler
Sep 12, 2000·Current Hypertension Reports·D T O'ConnorR J Parmer
Mar 10, 2001·Nature·E S LanderUNKNOWN International Human Genome Sequencing Consortium
Feb 19, 2002·Chemical Reviews·Torgeir Flatmark, Raymond C. Stevens
Apr 19, 2002·The Journal of Pharmacology and Experimental Therapeutics·Robert P Carson, David Robertson
Oct 19, 2002·Biological Psychology·Harold SniederFrank A Treiber
Nov 5, 2002·Nature Reviews. Genetics·Dorret BoomsmaLeena Peltonen
Dec 6, 2002·Nature·UNKNOWN Mouse Genome Sequencing ConsortiumEric S Lander
Jan 23, 2003·Twin Research : the Official Journal of the International Society for Twin Studies·Myles CockburnThomas M Mack
Jan 30, 2003·Psychosomatic Medicine·Frank A TreiberTeletia Taylor

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Citations

Jun 24, 2010·Cellular and Molecular Neurobiology·Fangwen RaoDaniel T O'Connor
Nov 26, 2010·Cellular and Molecular Neurobiology·Alberto Pérez-AlvarezAlmudena Albillos
Nov 26, 2010·Current Hypertension Reports·Kuixing ZhangDaniel T O'Connor
Jul 14, 2010·Forensic Science, Medicine, and Pathology·Siri H Opdal, Torleiv O Rognum
Jun 11, 2008·Chemico-biological Interactions·A M ValleP Taylor
Dec 12, 2012·Twin Research and Human Genetics : the Official Journal of the International Society for Twin Studies·Wendy CozenThomas M Mack
Jul 13, 2012·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Fokko J BoskerHarold Snieder
Oct 14, 2010·Nature Reviews. Genetics·Vikas BansalNicholas J Schork
Oct 13, 2006·Schizophrenia Bulletin·Nicholas J SchorkDavid L Braff
Feb 9, 2010·Journal of Hypertension·Sucheta M VaingankarDaniel T O'Connor
Apr 16, 2011·The Journal of Pharmacology and Experimental Therapeutics·Anne M VallePalmer Taylor
Feb 1, 2008·Journal of the American Society of Nephrology : JASN·Rany M SalemDaniel T O'Connor
Jan 20, 2009·Journal of Neurogenetics·Gary E Swan, Christina N Lessov-Schlaggar
Aug 14, 2009·Kidney International·Maple M FungDaniel T O'Connor
Dec 8, 2009·Neuroscience and Biobehavioral Reviews·Ting WuEco de Geus
Jan 6, 2009·Annals of the New York Academy of Sciences·Fangwen RaoDaniel T O'Connor
Oct 18, 2013·Neuropathology and Applied Neurobiology·Simon M L PaineNeil J Sebire
Jun 9, 2012·Journal of the American College of Cardiology·Jason T DavisDaniel T O'Connor
May 20, 2016·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Jeanne E SavageJohn M Hettema
Dec 25, 2016·Human Molecular Genetics·Beben BenyaminDaniel T O'Connor
Sep 25, 2010·American Journal of Hypertension·Maple M FungDaniel T O'Connor
Mar 10, 2017·Electrolyte & Blood Pressure : E & BP·Yu Ho LeeSang Ho Lee
Feb 1, 2006·Hypertension·Elizabeth O Lillie, Daniel T O'Connor

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