Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2006) 11 P368

ECE2006 Poster Presentations Diabetes, metabolism and cardiovascular (174 abstracts)

Estrogen receptor alpha (ER ‘alpha’) gene polymorphisms and first-ever primary intracerebral hemorrhage (PICH)

M Strand 1 , I Söderström 1 , P-G Wiklund 1 , G Hallmans 2 , L Weinehall 3 , S Söderberg 1 & T Olsson 1

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1Department of Public Health and Clinical Medicine, Medicine, Umeå University, Umeå, Sweden; 2Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden; 3Department of Public Health and Clinical Medicine, Epidemiology, Umeå University, Umeå, Sweden.


Context: Estrogens may have protective properties in the cardiovascular system, linked to the activation of estrogen receptor alpha (ERα), present in vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). ERα-mediated signaling regulates vasodilatation and atherogenesis, and since hypertension and atherosclerosis are major mechanisms in stroke development, we hypothesized that genetic variations in the ERα gene (ESR1) were associated with stroke.

Materials and methods: We performed a population-based prospective nested case-control study, in which the relationship between the ESR1 polymorphisms c.454-397T>C and c.454-351A>G and stroke were examined. Definitive first-ever stroke events (n=388), i.e. ischemic stroke (IS) (n=320), primary intracerebral hemorrhage (PICH) (n=61) and unspecified stroke (n=7) cases, and controls without cardiovascular disease (n=775), matched for age, sex, and geographical region were included. Traditional cardiovascular risk factors were obtained from all participants. Genotyping was performed using restriction fragment length polymorphism (RFLP) technique and allelic discrimination using the 5′nuclease assay.

Results: The unadjusted odds ratio (OR) for PICH was 2.19 (95% CI: 1.10–4.34) for carriers of the c.454-397T/T genotype compared with non-carriers. This association persisted after adjustment for established stroke risk markers (OR=3.58, 95% CI: 1.25–10.21). Carriers of either one or two alleles of c.454-397T also had significantly higher mean systolic (P=0.0046) and diastolic (P=0.0198) blood pressure than non-carriers did. The combinations of genotype c.454-397T/T and hypertension (OR=21.46, 95% CI: 5.20–88.51), high systolic (OR=18.17, 95% CI: 4.91–67.31) or diastolic blood pressure (OR=11.94, 95% CI=3.75–38.03) were strongly associated with increased risk of PICH, with synergy indices (SIs) for these combinations indicating significant positive interactions.

Conclusions: The genotype c.454-397T/T is associated with increased risk of PICH, particularly in combination with hypertension. This implies alterations in ERα-mediated signaling in the pathophysiology of PICH.

Volume 11

8th European Congress of Endocrinology incorporating the British Endocrine Societies

European Society of Endocrinology 
British Endocrine Societies 

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