Oestrogen receptor α gene polymorphism is related to aortic valve sclerosis in postmenopausal women

. Nordström P, Glader CA, Dahlén G, Slunga Birgander L, Lorentzon R, Waldenström A, Lorentzon M (Sports Medicine Unit; Department of Geriatric Medicine; Clinical Chemistry; Section of Cardiology; and National Institute for Working Life, Umeå, Sweden). Oestrogen receptor α gene polymorphism is related to aortic valve sclerosis in postmenopausal women. J Intern Med 2003; 254: 140–146. Objectives. Aortic valvular sclerosis (AS) is an inflammatory process and not a result of normal ageing. The sclerotic process is accelerated by risk factors such as smoking and high cholesterol levels. The genetic factors for the development of AS are however unknown. Therefore the purpose of the present study was to investigate whether polymorphisms in the oestrogen receptor α (ORα) gene and in the transforming growth factor β (TGF‐β1) gene were related to the presence of AS in postmenopausal women. Design. Case–control study. Subjects and methods. Relationships were tested between polymorphisms in the ORα gene defined by the restriction enzymes PvuII and XbaI, and in the TGF‐β1 gene defined by AocI, and AS, lipid levels, and lipoprotein(a) [Lp(a)] in 41 postmenopausal female patients and 41 age‐ and sex‐matched controls. These polymorphisms were also tested in relation to lipid levels and Lp(a), in 99 healthy Caucasian girls, aged 16.9 ± 1.2 years. Results. In the postmenopausal patients and age‐matched controls, the PvuII polymorphism was independently associated with an increased risk of AS [odds ratio (OR) = 3.38; 95% confidence interval (CI) 1.13–10.09). A genotype defined by at least one restriction site in the PvuII polymorphism and two restriction sites in the TGF‐β1 polymorphism was related to a highly significantly increased risk of AS (OR = 4.58; 95% CI 1.68–12.51). In the adolescent female cohort, presence of two restriction sites in the PvuII polymorphism was associated with higher levels of total cholesterol (TC) (P = 0.02), and low‐density lipoprotein cholesterol (LDL) (P = 0.04). Conclusions. We have demonstrated that the PvuII polymorphism in the ORα gene is related to both the presence of AS in postmenopausal women and to lipid levels in adolescent females, suggesting that this polymorphism may influence the risk of AS partly by affecting lipid levels.