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[白细胞介素-1基因簇多态性与强直性脊柱炎遗传易感性的荟萃分析]

[A meta-analysis on interleukin-1 gene cluster polymorphism and genetic susceptibility for ankylosing spondylitis].

作者信息

Wu Zhen, Gu Jie-ruo

机构信息

Department of Rheumatology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2007 Feb 13;87(7):433-7.

Abstract

OBJECTIVE

To investigate the association between interleukin (IL)-1 gene cluster polymorphism and the genetic susceptibility for ankylosing spondylitis (AS).

METHODS

Relevant published data were retrieved through Pubmed, EMBASE, Cochrane library and Chinese Bio-medicine Database (CBM). Studies eligible for this meta-analysis had to meet all the following inclusion criteria: (1) the content was associated with population-based case-control studies, (2) the study was on the relationship between the IL-1 gene cluster polymorphism and AS, (3) the diagnosis of AS was based on the modified New York criteria (1984) by the rheumatologist. (4) the raw data including the frequencies of alleles and certain genotypes in case and control groups could be collected. and (5) the distribution of studied loci in the populations was in accord with the Hardy-Weinberg equilibrium. Researches that didn't meet the inclusion criteria, as well as the duplicated reports, family-based studies were excluded. All analyses were conducted with the software 'Review Manager' Version 4.2.8.

RESULTS

(1) A total of 6 literatures, including 9 population samples, were studied. The overall combined data were verified to be heterogeneous, and the heterogeneity disappeared after stratification by the race. Then, the fixed-effect model could be applied. (2) The combined data revealed the frequencies of allele 2 and its genotypes of IL-1RN intron 2 variable number of tendem repeats were higher in the AS groups than in the controls in the Caucasian population (allele 2: OR=1.52, 95% CI=1.26 approximately 1.84, P<0.01; genotype: OR=1.33, 95% CI=1.04 approximately 1.70, P<0.05), but lower in the AS groups than in the controls in the Mongolian population (allele 2: OR=0.55, 95% CI=0.38 approximately 0.81, P<0.01; genotype: OR=0.51, 95% CI=0.34 approximately 0.77, P<0.01). (3) The minor allele T of IL-1A -889C>T (rs1800587) was higher in the AS group than in the controls in the Caucasian population (allele T: OR=1.36, 95% CI=1.12 approximately 1.66, P<0.01; genotype C/T+T/T: OR=1.56, 95% CI=1.20 approximately 2.03, P<0.01). This distribution could not be found in the Mongolian population for this SNP. (4) The minor allele G of IL-1F8 SNP (rs1900287) was higher in the AS group than in the controls in the Caucasian population (OR=1.22, 95% CI=1.04 approximately 1.44, P<0.05).

CONCLUSION

The genetic susceptibility for AS may be associated with the IL-1 gene cluster polymorphism. The relevant polymorphic sites include IL-1RN 86bp VNTR in intron 2, IL-1A -889C>T (rs1800587) and IL-1F8 SNP (rs1900287). Furthermore, there is a distinct discrepancy for this association among races.

摘要

目的

探讨白细胞介素(IL)-1基因簇多态性与强直性脊柱炎(AS)遗传易感性之间的关联。

方法

通过Pubmed、EMBASE、Cochrane图书馆和中国生物医学数据库(CBM)检索相关已发表数据。符合本荟萃分析的研究必须满足以下所有纳入标准:(1)内容与基于人群的病例对照研究相关;(2)研究IL-1基因簇多态性与AS的关系;(3)AS的诊断基于风湿病学家修订的纽约标准(1984年);(4)可收集病例组和对照组中包括等位基因频率和某些基因型频率的原始数据;(5)所研究位点在人群中的分布符合Hardy-Weinberg平衡。不符合纳入标准的研究以及重复报告、基于家系的研究均被排除。所有分析均使用“Review Manager”4.2.8版软件进行。

结果

(1)共研究了6篇文献,包括9个群体样本。总体合并数据经检验存在异质性,按种族分层后异质性消失,然后可应用固定效应模型。(2)合并数据显示,在白种人群中,AS组IL-1RN内含子2可变串联重复序列的等位基因2及其基因型频率高于对照组(等位基因2:OR = 1.52,95%CI = 1.26至1.84,P < 0.01;基因型:OR = 1.33,95%CI = 1.04至1.70,P < 0.05),但在蒙古族人群中,AS组低于对照组(等位基因2:OR = 0.55,95%CI = 0.38至0.81,P < 0.01;基因型:OR = 0.51,95%CI = 0.34至0.77,P < 0.01)。(3)在白种人群中,AS组IL-1A -889C>T(rs1800587)的次要等位基因T高于对照组(等位基因T:OR = 1.36,95%CI = 1.12至1.66,P < 0.01;基因型C/T + T/T:OR = 1.56,95%CI = 1.20至2.03,P < 0.01)。在蒙古族人群中未发现该单核苷酸多态性的这种分布。(4)在白种人群中,AS组IL-1F8单核苷酸多态性(rs1900287)的次要等位基因G高于对照组(OR = 1.22,95%CI = 1.04至1.44,P < 0.05)。

结论

AS的遗传易感性可能与IL-1基因簇多态性有关。相关多态性位点包括IL-1RN内含子2中的86bp VNTR、IL-1A -889C>T(rs1800587)和IL-1F8单核苷酸多态性(rs1900287)。此外,这种关联在不同种族之间存在明显差异。

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