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中国南方人群散发性阿尔茨海默病中肿瘤坏死因子-α(TNF-α)G-308A多态性的表达及基因分析

Expression and genetic analysis of tumor necrosis factor-alpha (TNF-alpha) G-308A polymorphism in sporadic Alzheimer's disease in a Southern China population.

作者信息

Yang Lianhong, Lu Ruiyan, Jiang Longyuan, Liu Zhonglin, Peng Ying

机构信息

Department of Neurology, The Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510120, PR China.

出版信息

Brain Res. 2009 Jan 9;1247:178-81. doi: 10.1016/j.brainres.2008.10.019. Epub 2008 Nov 1.

Abstract

Alzheimer's disease (AD) is one of most common chronic neurodegenerative diseases in the elderly. Tumor necrosis factor-alpha (TNF-alpha) was found elevated markedly in the serum and the cerebral spinal fluid of AD patients. And the elevation of TNF-alpha was thought to be associated with the occurrence of AD in China. However, it is still unclear whether the TNF-alpha polymorphism is related to the sporadic Alzheimer's disease (SAD) in China as well. Hence, in this study, we try to investigate the relationship between TNF-alpha G-308A polymorphism and its susceptibility to SAD in a Southern China population. The polymerase chain reaction-sequence specific primers (PCR-SSP) was performed to detect the frequencies of genotypes and alleles of TNF-alpha in 112 SAD patients and 121 controls. And the levels of TNF-alpha in serum were measured by radioimmunoassay. The differences of polymorphic distribution and the levels of TNF-alpha in serum between groups were then analyzed, and odds ratio was computed for association analysis. The frequency of A-allele was significantly increased in patients with SAD compared with that of the controls (chi(2)=4.256, P=0.039). A significantly increased risk of SAD was observed in the carriers of A-allele (OR=2.635, 95% CI 1.027-6.763, P<0.01). In parallel, the serum level of TNF-alpha in SAD group was much higher than that in control group (chi(2)=10.21, P=0.0042). And the elevation of serum level of TNF-alpha was closely associated with the risk of SAD (OR=3.542, 95% CI 2.304-8.854, P<0.05) as well. These results suggested that the TNF-alpha gene G-308A polymorphism might be a risk factor for SAD in Southern China. A-allele might play a role in the susceptibility of SAD.

摘要

阿尔茨海默病(AD)是老年人中最常见的慢性神经退行性疾病之一。在中国,肿瘤坏死因子-α(TNF-α)在AD患者的血清和脑脊液中显著升高,且TNF-α升高被认为与AD的发病有关。然而,TNF-α基因多态性是否也与中国散发性阿尔茨海默病(SAD)相关尚不清楚。因此,在本研究中,我们试图调查中国南方人群中TNF-α基因G-308A多态性与SAD易感性之间的关系。采用聚合酶链反应-序列特异性引物(PCR-SSP)技术检测112例SAD患者和121例对照者中TNF-α基因的基因型和等位基因频率,并用放射免疫法测定血清中TNF-α水平。然后分析两组间多态性分布及血清TNF-α水平的差异,并计算优势比进行关联分析。与对照组相比,SAD患者中A等位基因频率显著增加(χ2=4.256,P=0.039)。携带A等位基因者患SAD的风险显著增加(OR=2.635,95%可信区间1.027-6.763,P<0.01)。同时,SAD组血清TNF-α水平明显高于对照组(χ2=10.21,P=0.0042)。血清TNF-α水平升高也与SAD风险密切相关(OR=3.542,95%可信区间2.304-8.854,P<0.05)。这些结果提示,TNF-α基因G-308A多态性可能是中国南方SAD的一个危险因素,A等位基因可能在SAD易感性中起作用。

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