CCTTT pentanucleotide repeats in inducible nitric oxide synthase gene expression in patients with pulmonary arterial hypertension.
BACKGROUND
One of the pathways involved in pulmonary arterial hypertension (PAH) is the nitric oxide (NO) pathway. A polymorphism in the inducible NO synthase (NOS2) gene has been described, consisting of the CCTTT pentanucleotide repeat, which causes a reduction in NO production. The aim of this study was to determine if this polymorphism increases susceptibility to developing PAH.


METHODS
Sixty four patients with a diagnosis of PAH groupsi and iv and 50 healthy controls were compared. DNA genotyping of the samples for this polymorphism was performed using PCR. The distribution between both groups was compared and correlated with clinical and haemodynamic parameters and therapeutic response.


RESULTS
A significantly different distribution was observed in the number of repeats between patients and controls (P<.0001). When the samples were categorised by short forms (both alleles with less than 12repeats) and long forms (≥12 repeats), it was observed that the former had an almost 4-fold risk of developing PAH (odds ratio: 3.83; 95%CI: 1.19-12.32, P=.024). There were no differences between the most common types of PAH, either in therapeutic response or survival. There was no correlation between haemodynamic parameters and the number of repeats in the patients, and only a weak correlation with systolic PAH.


CONCLUSIONS
There are significant differences in the distribution of the NOS2 promotor CCTTT polymorphism between patients with PAH and the healthy population. A minor CCTTT pentanucleotide repeat in the NOS2 gene may increase the risk of developing PAH.
Servicio de Neumología, Complexo Hospitalario de Pontevedra, Pontevedra, España. Electronic address: adolfo.baloira.villar@sergas.es.
Adolfo
A
Baloira Villar
Departamento de Bioquímica, Genética e Inmunología, Facultad de Biología, Universidad de Vigo, Vigo, Pontevedra, España.
Guillermo
G
Pousada Fernández
Servicio de Neumología, Complexo Hospitalario de Vigo, Vigo, Pontevedra, España.
Carlos
C
Vilariño Pombo
Servicio de Neumología, Complexo Hospitalario de Pontevedra, Pontevedra, España.
Marta
M
Núñez Fernández
Servicio de Neumología, Hospital Marqués de Valdecilla, Santander, España.
Jose
J
Cifrián Martínez
Servicio de Neumología, Complexo Hospitalario de Pontevedra, Pontevedra, España.
Diana
D
Valverde Pérez
D005260:Female; D015870:Gene Expression; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D011110:Polymorphism, Genetic
C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II
Hipertensión arterial pulmonar; Nitric Oxide Synthase Type II; Nitric oxide; Polimorfismo; Polymorphism; Pulmonary arterial hypertension; Sintasa del óxido nítrico tipo II; Óxido nítrico