M235 → T polymorphism of the angiotensinogen gene predicts hypertension in the elderly

Objective: 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) ≤ 160 mmHg, diastolic blood pressure (DBP) < 90 mmHg) or systolic-diastolic hypertension (SDH:DBP ≤ 90 mmHg, SBP ≤ 160 mmHg) compared with normotensive controls (SBP < 160 mmHg, DBP < 90 mmHg). Design: A case-control study in 769 non-institutionalized, elderly (aged ≤ 60 years; female:male ratio 0.85) residents of Dubbo, New South Wales. Methods: 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. Results: 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; χ² = 6.0, P < 0.02) and the SDH group (0.62 and 0.38, respectively; χ² = 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). Conclusions: 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.