Alpha-adducin polymorphism, atherosclerosis, and cardiovascular and cerebrovascular risk.
OBJECTIVE
Carriers of the 460Trp allele of the alpha-adducin gene (ADD1) show higher rates of sodium reabsorption compared with homozygous carriers of the Gly460 allele and were found to have an increased risk of hypertension and cardiovascular disease. We studied the association between the Gly460Trp polymorphism and atherosclerosis, cardiovascular disease, and cerebrovascular disease.


METHODS
Intima-media thickness of the common carotid artery, as well as incident stroke and myocardial infarction, were studied within 6471 subjects of the Rotterdam Study. Within 1018 subjects of the Rotterdam Scan Study, prevalent silent brain infarcts and cerebral white matter lesions were studied. Subjects were grouped into 460Trp carriers (variant carriers) and homozygous carriers of the Gly460 allele (reference).


RESULTS
Intima-media thickness of the common carotid artery was 0.80 mm in variant carriers compared with 0.79 mm in the reference group (P=0.04). Variant carriers had an increased risk of any stroke (hazard ratio [HR], 1.22; 95% CI, 1.02 to 1.45), ischemic stroke (HR, 1.29; 95% CI, 1.02 to 1.63), hemorrhagic stroke (HR, 1.07; 95% CI, 0.59 to 1.92), and of myocardial infarction (HR, 1.33; 95% CI, 1.05 to 1.69). For any ischemic stroke, there was a significant interaction between the Gly460Trp polymorphism and hypertension. Variant carriers more often had a silent brain infarct (odds ratio, 1.36; 95% CI, 0.98 to 1.88) and had more subcortical white matter lesions than the reference group (1.45 vs1.24 mL; P=0.22).


CONCLUSIONS
The Gly460Trp polymorphism is associated with atherosclerosis, cardiovascular disease, and cerebrovascular disease, especially in hypertensive subjects.
van Rijn
Marie Josee E
MJ
Department of Epidemiology and Biostatistics, Erasmus Medical Center, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
Bos
Michiel J
MJ
Yazdanpanah
Mojgan
M
Isaacs
Aaron
A
Arias-Vásquez
Alejandro
A
Koudstaal
Peter J
PJ
Hofman
Albert
A
Witteman
Jacqueline C
JC
van Duijn
Cornelia M
CM
Breteler
Monique M B
MM
D000368:Aged; D050197:Atherosclerosis / Q000453:epidemiology / Q000235:genetics*; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics*; D002340:Carotid Artery Diseases / Q000453:epidemiology / Q000235:genetics; D002561:Cerebrovascular Disorders / Q000453:epidemiology / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics; D009426:Netherlands / Q000453:epidemiology; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000235:genetics; D000099291:Adducins
D002148:Calmodulin-Binding Proteins; D000099291:Adducins