Sex-specific effect of the alpha-adducin (G460W) and AGTR1 (A1166C) polymorphism on carotid intima-media thickness.
OBJECTIVE
In a primary care population covering a broad spectrum of cardiovascular risk (HIPPOCRATES project) the relationship between carotid intima-media thickness (CIMT) and six cardiovascular polymorphisms were analyzed in a cross-sectional study.


METHODS
CIMT was assessed in 618 participants, who were genotyped for the AGTR1 (A1166C), AGT (M235T), ACE (4656(rpt)), NOS3 (E298D), GNB3 (C825T) and ADD1 (G460W) polymorphisms. Linear regression analyses were performed to assess the relationship between CIMT and the polymorphisms.


RESULTS
The study population included 289 men (46.8%) and 329 (53.2%) women of whom 52.3% were treated with cardiovascular medication. CIMT was significantly associated with age, female sex, use of cardiovascular medication, waist circumference and dyslipidemia. After correction for these covariates, multivariate linear regression analyses showed that only in women the C-allele of AGTR1 was associated with a thicker CIMT (P = 0.03). The T-allele of ADD1 was associated with a smaller CIMT in both men and women, but this only reached statistical significance in women (P = 0.03).


CONCLUSIONS
Although the effect of both genetic variants on CIMT was small, this study showed a statistically significant effect of AGTR1 and ADD1 in women. However, our findings should be viewed as hypothesis-generating and require further confirmation in prospective epidemiological primary care studies.
Plat
Arian W
AW
Department of General Practice, School for Public Health and Primary Care (CAPHRI), The Netherlands.
Stoffers
Henri E J H
HE
de Leeuw
Peter W
PW
van Schayck
Constant P
CP
Soomers
Frank L
FL
Kester
Arnold D M
AD
Aretz
Karin
K
Kroon
Abraham A
AA
D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D012737:Sex Factors; D017539:Tunica Intima / Q000033:anatomy & histology*; D000099291:Adducins
D002148:Calmodulin-Binding Proteins; D044140:Receptor, Angiotensin, Type 1; D000099291:Adducins; C544065:AGTR1 protein, human