东亚人群NRAMP1基因多态性与结核易感性的Meta分析

Meta-analysis on NRAMP1 gene polymorphisms and tuberculosis susceptibility in East-Asia population

目的应用Meta分析探讨东亚人群NRAMP1基因3个多态性位点与结核易感性的关系。方法应用主题词和关键词“NRAMP1”、“SLC11A1”、“tuberculosis”和“结核”,检索1995年1 月至2005年5月Medline、Ovid及CBM disc数据库发表的有关文献,并辅以文献追溯的方法。结果结核病组和对照组3’UTR、D543N和INT4位点的多态现象同最常见纯合子基因型频率比值比 (OR)的合并OR值分别为1．68(95％CI:1．31-2．16,P<0．001);1．78(95％CI:1．38-2．30,P< 0．001);1．56(95％CI:0．72-3．35,P=0．26)。Egger线性回归分析提示3’UTR和D543N基因型相关文献没有发表偏倚,INT4基因型相关文献有一定的出版偏倚。结论东亚人群NRAMP1基因3’ UTR和D543N多态性位点与结核易感性相关;INT4多态性位点与结核易感性无统计学意义。

Objective To provide a quantitative summary in estimating the association between polymorphisms of 3 loci in NRAMP1 gene and susceptibility to tuberculosis in East-Asla population by means of meta analysis. Methods We searched databases （MEDLINE,OVID and CBM disc） from January 1995 to May 2005 using ＂NRAMP 1＂ or ＂SLC11A 1 ＂, in combination with ＂tuberculosis＂, also performed a manual search of citations from relevant original studies and literature. For each study involved, information was collected concerning the characteristics of the subjects, such as mean age of cases and the size of study. These characteristics were used to evaluate the sources of variation. Summary ORs and corresponding 95 % CI were estimated by fixed effects （Mantel-Haenszel） or random effects （DerSimonian and Laird） model. To check for publication bias,a funnel plot, using Egger＇s linear regression method, was constructed. Cumulative recta-analysis was performed to evaluate whether the summary OR for studies with the polymorphisms of the 3 loci in the NRAMP1 gene was changing along with the accumulation of more data. Chi-square goodness of fit was used to test deviation from Hardy-Weinberg equilibrium. Results Eight publications, with the number of cases and controls of 1067 and 1084 respectively, were identified and all genotype frequencies were consistent with Hardy-Weinberg equilibrium. The summary ORs for studies with polytnorphisms of 3＇ UTR, D543N and INT4 loci of the NRAMP1 gene among the East-Asia populatlonwere 1.68（95% CI. 1.31-2.16, P〈 0.001）, 1.78 （95% CI： 1.38-2.30, P〈 0.001 ）, 1.56 （95% CI. 0.72- 3.35, P- 0.26 ） , respectively when compared with their corresponding common homozygotes. Publication bias was not found in the studles with the three loci, except for INT4 locus, by Egger linear regression method. The cumulative summary effects OR s were 1.85 （ P - 0.02） in 2000,1.35 （P = 0.12） in 2002,1.64 （ P = 0. 001 ） in 2003, and 1.68 （ P〈 0. 001 ） in 2004 for 3＇ UTR locus, 1.88 （P=0.001） in 2000,1.65（P-0.001） in2002,1.70（P〈0.001） in 2003,1.76（P〈0.001） in 2004, and 1.78（P〈0.001） in 2005 for D543N locus,and 0.88（P=0：70） in 2002,2.50（P= 0.41） in 2003, 1.52（P-0.42） in 2004 and 1.56（P=0.26） in 2005 for INT4 loucs. Conclusion Polymorphisms at 3＇ UTR and D543N loci had statistically significant association between the NRAMP1 variants and susceptibility to tuberculosis in the East-Asla descendants, and variant in the INT4 locus failed to show statistically significant association in the East-Asia population.