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(Hypertension. 2003;41:1202.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Angiotensinogen Single Nucleotide Polymorphisms, Elevated Blood Pressure, and Risk of Cardiovascular Disease

Amar A. Sethi; Børge G. Nordestgaard; Marie-Louise M. Grønholdt; Rolf Steffensen; Gorm Jensen; Anne Tybjærg-Hansen

From the Department of Clinical Biochemistry, Herlev University Hospital (A.A.S., B.G.N.); the Copenhagen City Heart Study, Bispebjerg University Hospital (B.G.N., G.J., A.T.-H.); the Department of Vascular Surgery, Gentofte University Hospital (M.-L.M.G.); the Department of Medicine B, Hillerød Hospital (R.S.); and the Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital (A.T.-H.); Copenhagen, Denmark.

Correspondence to Anne Tybjærg-Hansen, MD, DMSc, Department of Clinical Biochemistry, KB3011, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. E-mail at-h{at}rh.dk

In this study of 10 690 individuals, associations with elevated blood pressure, ischemic heart disease, and ischemic cerebrovascular disease were determined for two noncoding [A(-20)C, G(-6)A] and two coding (T174M, M235T) single nucleotide polymorphisms, analyzed alone and in combination (haplotypes). Participants from the general population with (n=4950) and without (n=4234) elevated blood pressure were compared (study 1), as were participants from the general population without ischemic heart disease and ischemic cerebrovascular disease (n=7965) and cases with either ischemic heart disease (n=1850, study 2) or ischemic cerebrovascular disease (n=848, study 3). Finally, 22-year follow-up of 9184 individuals from the general population examined risk of ischemic heart disease (study 4) and ischemic cerebrovascular disease (study 5). Individuals with -6AA, 174TT, or 235TT had plasma angiotensinogen levels increased by 80 ng/mL (P=0.01 and 0.05 for women and men) compared with individuals with -6GG, 174TT, or 235 MM. In women, this difference was associated with an odds ratio of elevated blood pressure of 1.25 (1.03 to 1.51), which increased to 1.63 (1.05 to 2.51) in postmenopausal women receiving hormone replacement therapy. The promoter single nucleotide polymorphisms alone or as haplotypes did not predict the continuous variables of systolic, diastolic, or pulse pressure in cross section or the risk of ischemic heart disease or ischemic cerebrovascular disease in either gender in case-control or prospective studies. Individuals with -6AA, 174TT, or 235TT in the angiotensinogen gene have increased plasma angiotensinogen levels and moderately increased risk of elevated blood pressure (women only) but unaltered blood pressure examined as a continuous variable and unaltered risk of ischemic heart disease and ischemic cerebrovascular disease.

Key Words: blood pressure • hypertension, genetic • cardiovascular diseases • cerebrovascular disorders

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