Wang Ji-Guang, Staessen Jan A, Barlassina Cristina, Fagard Robert, Kuznetsova Tatiana, Struijker-Boudier Harry A, Zagato Laura, Citterio Lorena, Messaggio Elisabetta, Bianchi Giuseppe
Studiecoördinatiecentrum, Hypertensie en Cardiovasculaire Revalidatie Eenheid, Departement voor Moleculair en Cardiovasculair Onderzoek, Katholieke Universiteit Leuven, Leuven, Belgium.
Kidney Int. 2002 Dec;62(6):2152-9. doi: 10.1046/j.1523-1755.2002.00691.x.
The substitution of tryptophan for glycine at amino acid 460 (Gly460Trp polymorphism) of the alpha-subunit of the heterodimeric cytoskeleton protein adducin increases renal sodium reabsorption and may be involved in the pathophysiology of essential hypertension. In the present study, we investigated in multivariate analyses whether the risk of hypertension was associated with the C1797T polymorphism of the beta-adducin gene.
A total of 1848 subjects randomly selected from a white population were genotyped. Study nurses measured blood pressure at the participants' homes.
The frequencies of the alpha-adducin Trp and beta-adducin T alleles were 0.23 and 0.11, respectively. In men (N = 904), the beta-adducin T allele was not associated with hypertension [adjusted relative risk (RR) vs. CC homozygotes 0.94, P = 0.77], but T allele carriers had lower plasma renin activity (PRA) and 24-hour urinary aldosterone excretion (P < 0.04). In all women (N = 944), beta-adducin T allele carriers had a higher risk of hypertension than CC homozygotes (RR 1.81, CI 1.18-2.77, P = 0.007), but similar PRA and 24-hour urinary aldosterone excretion (P> 0.29). In 345 post-menopausal women and 190 users of oral contraceptives, the RRs of hypertension were 2.47 (CI 1.34-4.64, P = 0.003) and 2.56 (CI 0.83-7.86, P = 0.10), respectively. For systolic pressure in women, there was a significant interaction (P = 0.02) between the alpha- and beta-adducin polymorphisms. Only in female carriers of the mutated alpha-adducin Trp allele was the systolic pressure significantly higher in beta-adducin T allele carriers compared with CC homozygotes (+3.8 mm Hg, P = 0.02). Furthermore, in the presence of the mutated alpha-adducin Trp allele, the RRs associated with the beta-adducin T allele were 2.35 (P = 0.01) in all women, 2.92 (P = 0.03) in post-menopausal subjects, and 3.79 (P = 0.09) in users of oral contraceptives.
The 1797T allele of the beta-adducin gene is associated with increased risk of hypertension in post-menopausal women and in users of oral contraceptives, particularly in the presence of the mutated alpha-adducin Trp allele. We hypothesize that inhibition of the renin-aldosterone system in men and absence of such a compensatory mechanism in women may explain, at least to some extent, the sexual dimorphism of the blood pressure phenotype in relation to the C1797T beta-adducin polymorphism.
在异二聚体细胞骨架蛋白内收蛋白的α亚基的第460位氨基酸处用色氨酸替代甘氨酸（甘氨酸460色氨酸多态性）会增加肾脏对钠的重吸收，可能参与原发性高血压的病理生理过程。在本研究中，我们在多变量分析中调查了高血压风险是否与β-内收蛋白基因的C1797T多态性相关。
从白人人群中随机选取1848名受试者进行基因分型。研究护士在参与者家中测量血压。
α-内收蛋白色氨酸和β-内收蛋白T等位基因的频率分别为0.23和0.11。在男性（N = 904）中，β-内收蛋白T等位基因与高血压无关[校正相对风险（RR）与CC纯合子相比为0.94，P = 0.77]，但T等位基因携带者的血浆肾素活性（PRA）和24小时尿醛固酮排泄量较低（P <0.04）。在所有女性（N = 944）中，β-内收蛋白T等位基因携带者患高血压的风险高于CC纯合子（RR 1.81，CI 1.18 - 2.77，P = 0.007），但PRA和24小时尿醛固酮排泄量相似（P> 0.29）。在345名绝经后女性和190名口服避孕药使用者中，高血压的RR分别为2.47（CI 1.34 - 4.64，P = 0.003）和2.56（CI 0.83 - 7.86，P = 0.10）。对于女性的收缩压，α-和β-内收蛋白多态性之间存在显著相互作用（P = 0.02）。仅在突变的α-内收蛋白色氨酸等位基因的女性携带者中，β-内收蛋白T等位基因携带者的收缩压与CC纯合子相比显著更高（+3.8 mmHg，P = 0.02）。此外，在存在突变的α-内收蛋白色氨酸等位基因的情况下，与β-内收蛋白T等位基因相关的RR在所有女性中为2.35（P = 0.01），在绝经后受试者中为2.92（P = 0.03），在口服避孕药使用者中为3.79（P = 0.09）。
β-内收蛋白基因的1797T等位基因与绝经后女性和口服避孕药使用者患高血压的风险增加相关，特别是在存在突变的α-内收蛋白色氨酸等位基因的情况下。我们假设男性肾素 - 醛固酮系统的抑制以及女性缺乏这种代偿机制可能至少在一定程度上解释了与C1797Tβ-内收蛋白多态性相关的血压表型中的性别差异。
