Severity of cardiovascular disease in postmenopausal women: associations with common estrogen receptor alpha polymorphic variants.
OBJECTIVE
Impaired estrogen action is a risk factor for coronary artery disease (CAD). Associations of CAD with estrogen receptor alpha (ER alpha) polymorphisms, which may influence sensitivity to estrogen, have been reported for men; the data concerning women are not conclusive. We investigated the association of common ER alpha polymorphisms with the severity of CAD and with metabolic and reproductive factors in postmenopausal women undergoing coronary angiography.


METHODS
ER alpha polymorphisms at positions c.454-397 T>C (PvuII) and c.454-351 A>G (XbaI) were studied in 157 women (age 45-88 years). The severity of CAD was assessed by the number of arteries with >50% stenosis in the angiography.


RESULTS
There was a significant association between the TT, TC, and CC genotypes (PvuII) and the severity of CAD (P=0.008); similar results were obtained for the XbaI polymorphism (P=0.021). These associations were independent of other risk factors for CAD. Women homozygous for the C allele had significantly higher triglyceride and insulin levels; they belonged more frequently to the group with a low number of births (n</=1; P=0.014, Fisher's exact).


CONCLUSIONS
Common ER alpha polymorphisms may influence the severity of CAD in women undergoing coronary angiography, reflecting lifetime exposure to estrogen. Similar associations have been reported for men with CAD. These polymorphisms should probably be taken into account when associations with estrogenic actions are examined.
Alevizaki
M
M
Endocrine Unit, Evgenidion Hospital, Athens University School of Medicine, Athens, Greece. mani@otenet.gr
Saltiki
K
K
Cimponeriu
A
A
Kanakakis
I
I
Xita
N
N
Alevizaki
C C
CC
Georgiou
I
I
Sarika
H-L
HL
D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001723:Birth Rate; D002318:Cardiovascular Diseases / Q000000981:diagnostic imaging* / Q000235:genetics*; D017023:Coronary Angiography; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007328:Insulin / Q000097:blood; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017698:Postmenopause; D012720:Severity of Illness Index; D014280:Triglycerides / Q000097:blood
D047628:Estrogen Receptor alpha; D007328:Insulin; D014280:Triglycerides