TY - JOUR
T1 - Atrial Natriuretic Peptide Gene Polymorphisms and Risk of Ischemic Stroke in Humans
AU - Rubattu, Speranza
AU - Stanzione, Rosita
AU - Di Angelantonio, Emanuele
AU - Zanda, Bastianina
AU - Evangelista, Anna
AU - Tarasi, David
AU - Gigante, Bruna
AU - Pirisi, Angelo
AU - Brunetti, Ercole
AU - Volpe, Massimo
PY - 2004/4
Y1 - 2004/4
N2 - Background and Purpose - 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.
AB - Background and Purpose - 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.
KW - Cerebrovascular disorders
KW - Gene mutation
KW - Genetics
KW - Natriuretic peptides, atrial
KW - Receptors, atrial natriuretic factor
UR - http://www.scopus.com/inward/record.url?scp=12144291230&partnerID=8YFLogxK
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U2 - 10.1161/01.STR.0000119381.52589.AB
DO - 10.1161/01.STR.0000119381.52589.AB
M3 - Article
C2 - 15017020
AN - SCOPUS:12144291230
VL - 35
SP - 814
EP - 818
JO - Stroke
JF - Stroke
SN - 0039-2499
IS - 4
ER -