肿瘤坏死因子-α基因G-308A多态性与C反应蛋白水平相关：遗产家庭研究。

The TNF-alpha G-308A polymorphism is associated with C-reactive protein levels: the HERITAGE Family Study.

作者信息

Lakka Hanna-Maaria, Lakka Timo A, Rankinen Tuomo, Rice Treva, Rao D C, Leon Arthur S, Skinner James S, Bouchard Claude

机构信息

Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Road, Baton Rouge, Louisiana 70808-4124, USA.

出版信息

Vascul Pharmacol. 2006 May;44(5):377-83. doi: 10.1016/j.vph.2006.02.002. Epub 2006 Mar 3.

DOI:10.1016/j.vph.2006.02.002

PMID:16581306

Abstract

OBJECTIVE

Pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha), stimulate the release of C-reactive protein (CRP). We investigated the association between the TNF-alpha G-308A polymorphism and plasma CRP levels.

METHODS

Subjects were 456 White (225 men, 231 women) and 232 Black (83 men, 149 women) healthy adults who underwent a 20-week standardized exercise program in the HERITAGE Family Study. The TNF-alpha gene promoter polymorphism was determined using PCR amplification followed by NcoI digestion. Plasma CRP was measured using a high-sensitivity assay.

RESULTS

Genotype frequencies were in Hardy-Weinberg equilibrium. After adjustment for age, smoking, alcohol consumption, maximal oxygen uptake and, in women, hormone use, the AA homozygotes for the G-308A polymorphism had higher baseline CRP levels than other genotypes in White and Black men (P<0.001 and P = 0.044, respectively) and in Black women (P = 0.032). Body mass index partly explained these associations in Blacks. The exercise program results provided further evidence for an association with the polymorphism. Among those with high CRP at baseline (> or = 3.0 mg/L), regular exercise decreased CRP less in AA homozygotes than in other genotypes (P = 0.043).

CONCLUSION

The AA genotype of the TNF-alpha G-308A polymorphism is associated with higher plasma CRP levels and less favorable CRP response to regular exercise.

摘要

目的

促炎细胞因子，如肿瘤坏死因子α（TNF-α），可刺激C反应蛋白（CRP）的释放。我们研究了TNF-α基因G-308A多态性与血浆CRP水平之间的关联。

方法

在HERITAGE家族研究中，456名白人（225名男性，231名女性）和232名黑人（83名男性，149名女性）健康成年人参与了一项为期20周的标准化运动计划。采用PCR扩增后NcoI酶切法测定TNF-α基因启动子多态性。使用高灵敏度检测法测量血浆CRP。

结果

基因型频率处于Hardy-Weinberg平衡状态。在对年龄、吸烟、饮酒、最大摄氧量以及女性的激素使用情况进行调整后，G-308A多态性的AA纯合子在白人和黑人男性（分别为P<0.001和P = 0.044）以及黑人女性（P = 0.032）中的基线CRP水平高于其他基因型。体重指数在一定程度上解释了黑人中的这些关联。运动计划结果为该多态性的关联提供了进一步证据。在基线CRP水平较高（≥3.0 mg/L）的人群中，规律运动使AA纯合子的CRP降低幅度小于其他基因型（P = 0.043）。