高血压严重程度对PGC-1α基因与血压及高血压风险关联的影响。
The impact of severity of hypertension on association of PGC-1alpha gene with blood pressure and risk of hypertension.
作者信息
Xie Gaoqiang, Guo Dongshuang, Li Ying, Liang Shengying, Wu Yangfeng
机构信息
Department of Epidemiology, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, The National Center for Cardiovascular Disease Control and Research, China.
出版信息
BMC Cardiovasc Disord. 2007 Oct 31;7:33. doi: 10.1186/1471-2261-7-33.
BACKGROUND
Little is known about the impact of severity of hypertension on the association of genes with high blood pressure, which may cause the inconsistently reported associations of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) gene with blood pressure.
METHODS
A cardiovascular epidemiology survey and genotyping were performed in a population-based sample of 1642 apparently healthy residents (648 men and 994 women aged 35-91 years).
RESULTS
After adjusting for age, sex, body mass index, and antihypertensive medication, G482S and +2962A/G polymorphisms were significantly associated with systolic blood pressures in hypertension patients with medication use (p = 0.023 and 0.022 for G482S and +2962A/G respectively) but not in all participants, normotensives, and patients with no medication use. Multivariable logistic models showed that the two polymorphisms were significantly associated with severe hypertension (SBP > or = 160 mm Hg or DBP > or = 100 mm Hg regardless of medication use), with an OR of 0.6(95% confidence interval [CI]: 0.4-0.98) for S482S vs. G482G and an OR of 1.9(95% CI: 1.2-3.0) for +2962G/G vs. +2962A/A, but not with regular hypertension (SBP > or = 140 mm Hg or DBP > or = 90 mm Hg or current use of antihypertensive medications), with an OR of 0.9(95% CI: 0.7-1.2) for S482S vs. G482G and an OR of 0.9(95% CI: 0.7-1.4) for +2962G/G vs. +2962A/A. Haplotype combination analyses showed a significant synthetic effect (OR of severe hypertension for persons with G482X and +2962G/G = 2.6, 95%CI: 1.5-4.4, with reference to persons with S482S and +2962A/X).
CONCLUSION
In this study, we found that G482S and +2962A/G polymorphisms of PGC-1alpha gene were only significantly associated with severe hypertension defined by occasional clinic blood pressure measurements. This finding suggested severe hypertension rather than regular hypertension should be used as the outcome in studies on association of genes with blood pressure or hypertension, in order to have a better power.
背景
高血压严重程度对基因与高血压关联的影响鲜为人知，这可能导致过氧化物酶体增殖物激活受体γ辅激活因子1α（PGC - 1α）基因与血压的关联报道不一致。
方法
对1642名表面健康的居民（648名男性和994名女性，年龄35 - 91岁）进行了基于人群的心血管流行病学调查和基因分型。
结果
在调整年龄、性别、体重指数和抗高血压药物使用情况后，G482S和 + 2962A/G多态性与正在使用药物的高血压患者的收缩压显著相关（G482S和 + 2962A/G的p值分别为0.023和0.022），但在所有参与者、血压正常者和未使用药物的患者中并非如此。多变量逻辑模型显示，这两种多态性与重度高血压（收缩压≥160 mmHg或舒张压≥100 mmHg，无论是否使用药物）显著相关，S482S与G482G相比，比值比（OR）为0.6（95%置信区间[CI]：0.4 - 0.98），+ 2962G/G与 + 2962A/A相比，OR为1.9（95% CI：1.2 - 3.0），但与普通高血压（收缩压≥140 mmHg或舒张压≥90 mmHg或当前使用抗高血压药物）无关，S482S与G482G相比，OR为0.9（95% CI：0.7 - 1.2），+ 2962G/G与 + 2962A/A相比，OR为0.9（95% CI：0.7 - 1.4）。单倍型组合分析显示出显著的综合效应（G482X和 + 2962G/G个体患重度高血压的OR = 2.6，95%CI：1.5 - 4.4，参照S482S和 + 2962A/X个体）。
结论
在本研究中，我们发现PGC - 1α基因的G482S和 + 2962A/G多态性仅与通过偶尔的临床血压测量定义的重度高血压显著相关。这一发现表明，在基因与血压或高血压关联研究中，为了获得更好的检验效能，应将重度高血压而非普通高血压作为研究结果。
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