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To determine whether the M235→T polymorphism (exon 2) of the angiotensinogen gene is associated with hypertension in elderly patients with isolated systolic hypertension [ISH: systolic blood pressure (SBP) ≥ 160mmHg, diastolic blood pressure (DBP)<90mmHg) or systolic-diastolic hypertension (SDH: DBP ≥ 90 mmHg, SBP ≥ 160 mmHg) compared with normotensive controls (SBP<160 mmHg, DBP<90 mmHg).A case-control study in 769 non-institutionalized, elderly (aged ≥ 60 years; female: male ratio 0.85) residents of Dubbo, New South Wales.Individuals were classified as having ISH (n=171), having SDH (n=218) and being normotensive controls (n=366) with age and sex matching. MM, TT and MT genotypes were determined by a nested polymerase chain reaction strategy using DNA extracted from serum. The prediction of ISH or SDH by genotype or allele was examined in a multiple-logistic regression model that controlled for various confounders.SBP (mean ± SD, mmHg)/DBP (mean ± SD, mmHg) was 176 ± 16/79 ± 8 in the ISH group, 167 ± 23/97 ± 7 in the SDH group and 134 ± 14/74 ± 9 in the normotensive control group. The frequencies of M and T alleles in the normal population (0.69 and 0.31, respectively) were altered significantly in the ISH group (0.61 and 0.39, respectively; X2=6.0, P<0.02) and the SDH group (0.62 and 0.38, respectively; X2=6.0, P<0.02). The presence of the TT genotype predicted both ISH (odds ratio 1.9, 95% confidence interval 1.1-3.3) and SDH (1.7,1.0-3.0) as did that of the T allele (ISH: 1.3,1.0-1.7; SDH: 1.3,1.0-1.7).The M235→T polymorphism may be a marker for both forms of hypertension in the elderly. Whether the TT genotype represents a genetic risk factor for the development of hypertension in later life requires confirmation.