肿瘤坏死因子-α微卫星多态性与印度类风湿关节炎患者的相关性

Tumor necrosis factor-alpha microsatellite polymorphism association with rheumatoid arthritis in Indian patients.

作者信息

Agrawal Charu, Raghav Sunil Kumar, Gupta Bhawna, Das Rakha Hari, Chaturvedi Ved Prakash, Goswami Kalyan, Das Hasi Rani

机构信息

Institute of Genomics & Integrative Biology, Delhi University Campus, Delhi, India.

出版信息

Arch Med Res. 2005 Sep-Oct;36(5):555-9. doi: 10.1016/j.arcmed.2005.03.035.

DOI:10.1016/j.arcmed.2005.03.035

PMID:16099338

Abstract

BACKGROUND

Level of TNF-alpha increases significantly in synovial fluid of rheumatoid arthritis (RA) patients. It is proposed that tumor necrosis factor (TNF) microsatellite alleles may influence its expression and presumably can contribute to the disease severity. However, there is a lack of such study to predict any such association with RA in an Indian population.

METHODS

In this study, we investigated the differential pattern of distribution of TNF microsatellite alleles in an Indian population and its association with RA. One hundred eighteen RA patients and 120 healthy individuals were genotyped for TNF microsatellite alleles using Genescan. Odds ratio was calculated to demonstrate the correlation between allelic distribution and clinical severity.

RESULTS

The study shows that distribution of TNF microsatellite alleles in an Indian population is very different from other Asian Oriental and Western populations, except for some similarities with an Italian population. Frequency of microsatellite TNFd3 allele (9.24 vs. 3.85%, chi(2)=5.6, p < or =0.0179, OR=0.393, 95% CI=0.177-0.87) and more interestingly TNFd3 containing haplotypes has been found significantly reduced in patients. On the contrary, TNFb5 allele frequency increased in the patients (22.3 vs. 30.8%, chi(2)=4.4, p < or =0.036, OR=1.55, 95% CI=1.027-2.344) as compared to controls. Furthermore, significant increase in frequency of this allele in severe patients (22.3 vs. 33.8%, chi(2)=6.22, p < or =0.013, OR=1.78, 95% CI=1.132-2.798) along with the significant increase in haplotypes containing this allele supports the association of TNFb5 with disease severity.

CONCLUSIONS

In an Indian population, TNFb5 may be considered as a risk factor, whereas TNFd3, unlike others, may be protective for RA.

摘要

背景

类风湿关节炎（RA）患者滑液中肿瘤坏死因子-α（TNF-α）水平显著升高。有研究表明肿瘤坏死因子（TNF）微卫星等位基因可能影响其表达，并可能与疾病严重程度相关。然而，在印度人群中缺乏此类预测RA相关性的研究。

方法

在本研究中，我们调查了印度人群中TNF微卫星等位基因的差异分布模式及其与RA的相关性。使用基因扫描技术对118例RA患者和120例健康个体进行TNF微卫星等位基因基因分型。计算优势比以证明等位基因分布与临床严重程度之间的相关性。

结果

研究表明，印度人群中TNF微卫星等位基因的分布与其他亚洲东方和西方人群非常不同，但与意大利人群有一些相似之处。微卫星TNFd3等位基因频率（9.24%对3.85%，χ²=5.6，p≤0.0179，OR=0.393，95%CI=0.177-0.87），更有趣的是，在患者中发现含TNFd3的单倍型显著减少。相反地，与对照组相比，患者中TNFb5等位基因频率增加（22.3%对30.8%，χ²=4.4，p≤0.036，OR=1.55，95%CI=1.027-2.344）。此外，该等位基因在重症患者中的频率显著增加（22.3%对33.8%，χ²=6.22，p≤0.013，OR=1.78，95%CI=1.132-2.798），并且含该等位基因的单倍型显著增加支持了TNFb5与疾病严重程度的相关性。