Machado, Rajiv D. and Koehler, Rolf and Glissmeyer, Eric and Veal, Colin and Suntharalingam, Jay and Kim, Miryoung and Carlquist, John and Town, Margaret and Elliott, C. Gregory and Hoeper, Marius and Fijalkowska, Anna and Kurzyna, Marcin and Thomson, Jennifer R. and Gibbs, Simon R. and Wilkins, Martin R. and Seeger, Werner and Morrell, Nicholas W. and Gruenig, Ekkehard and Trembath, Richard C. and Janssen, Bart (2006) Genetic association of the serotonin transporter in pulmonary arterial hypertension. American journal of respiratory and critical care medicine, 173 (7). pp. 793-797. ISSN 1535-4970

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Abstract

RATIONALE: The bone morphogenetic receptor type II gene is the major genetic determinant for the inherited form of pulmonary arterial hypertension. However, deleterious mutations of this gene are not observed in the majority of subjects who develop the condition spontaneously and familial disease displays age- and sex-dependent penetrance, indicating the requirement for additional environmental and/or genetic modifiers for disease development. METHODS: We investigated polymorphic variation of the serotonin transporter gene, a biological candidate for predisposition to this vascular disorder. RESULTS: No significant evidence of association between alleles of the serotonin transporter gene and pulmonary hypertension was detected, nor did we observe a relationship with age of onset in familial and idiopathic disease. CONCLUSIONS: Variation of the serotonin transporter gene appears unlikely to confer significant susceptibility to pulmonary arterial hypertension. This study emphasizes the need for adequately powered cohorts for association analyses to identify not only genetic determinants of disease susceptibility but also inherited modifiers for disease development.

Item Type:	Article
Additional Information:	RATIONALE: The bone morphogenetic receptor type II gene is the major genetic determinant for the inherited form of pulmonary arterial hypertension. However, deleterious mutations of this gene are not observed in the majority of subjects who develop the condition spontaneously and familial disease displays age- and sex-dependent penetrance, indicating the requirement for additional environmental and/or genetic modifiers for disease development. METHODS: We investigated polymorphic variation of the serotonin transporter gene, a biological candidate for predisposition to this vascular disorder. RESULTS: No significant evidence of association between alleles of the serotonin transporter gene and pulmonary hypertension was detected, nor did we observe a relationship with age of onset in familial and idiopathic disease. CONCLUSIONS: Variation of the serotonin transporter gene appears unlikely to confer significant susceptibility to pulmonary arterial hypertension. This study emphasizes the need for adequately powered cohorts for association analyses to identify not only genetic determinants of disease susceptibility but also inherited modifiers for disease development.
Keywords:	Pulmonary arterial hypertension, 5-HTT
Subjects:	C Biological Sciences > C431 Medical Genetics
Divisions:	College of Sciences > Faculty of Science > School of Life Sciences
Depositing User:	Rajiv Machado
Date Deposited:	30 Sep 2012 20:18
Last Modified:	13 Mar 2013 09:15
URI:	http://eprints.lincoln.ac.uk/id/eprint/6320

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