Atrial natriuretic peptide gene polymorphisms and risk of ischemic stroke in humans.
OBJECTIVE
A precise definition of genetic factors responsible for common forms of stroke is still lacking. The purpose of the present study was to investigate the contributory role of the genes encoding atrial natriuretic peptide (ANP) and type A natriuretic peptide receptor (NPRA) in humans' susceptibility to develop ischemic stroke.


METHODS
Allele and genotype frequencies of ANP and NPRA were characterized in an Italian case-control study with patients affected by vascular disease or risk factors. Subjects were recruited from the island of Sardinia (206 cases, 236 controls).


RESULTS
A significant association between the ANP/TC2238 polymorphic site and stroke occurrence was found when a recessive model of inheritance was assumed. The risk conferred by this mutant genotype, when estimated by multivariate logistic regression analysis, was 3.8 (95% confidence interval, 1.4 to 10.9). A significantly increased risk of stroke recurrence was observed among cases carrying the ANP/CC2238 genotype compared with cases carrying the ANP/TT2238 genotype (P=0.04). No direct association of NPRA with stroke occurrence was detected. However, a significant epistatic interaction between the ANP/CC2238 genotype and an allelic variant of NPRA led to a 5.5-fold increased risk of stroke (95% confidence interval, 1.5 to 19.4).


CONCLUSIONS
Our findings support a direct contributory role of ANP to stroke in humans. A significant interaction between ANP and NPRA on stroke occurrence was found.
Rubattu
Speranza
S
IRCCS Neuromed, Localitá Camerelle, 86077 Pozzilli, Italy. rubattu.speranza@neuromed.it
Stanzione
Rosita
R
Di Angelantonio
Emanuele
E
Zanda
Bastianina
B
Evangelista
Anna
A
Tarasi
David
D
Gigante
Bruna
B
Pirisi
Angelo
A
Brunetti
Ercole
E
Volpe
Massimo
M
D000368:Aged; D009320:Atrial Natriuretic Factor / Q000235:genetics*; D002545:Brain Ischemia / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006162:Guanylate Cyclase / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics; D012008:Recurrence; D020521:Stroke / Q000453:epidemiology / Q000235:genetics*
D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A