Genetic association of the serotonin transporter in pulmonary arterial hypertension.
BACKGROUND
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.
Machado
Rajiv D
RD
Division of Medical Genetics, Department of Genetics, University of Leicester, Leicester, UK.
Koehler
Rolf
R
Glissmeyer
Eric
E
Veal
Colin
C
Suntharalingam
Jay
J
Kim
Miryoung
M
Carlquist
John
J
Town
Margaret
M
Elliott
C Gregory
CG
Hoeper
Marius
M
Fijalkowska
Anna
A
Kurzyna
Marcin
M
Thomson
Jennifer R
JR
Gibbs
Simon R
SR
Wilkins
Martin R
MR
Seeger
Werner
W
Morrell
Nicholas W
NW
Gruenig
Ekkehard
E
Trembath
Richard C
RC
Janssen
Bart
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics* / Q000378:metabolism; D007223:Infant; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D004247:DNA