Genetic polymorphisms of exon 1 of MBL2 contribute to tuberculosis risk especially in Asian populations: an updated meta-analysis of 26 studies

Abstract

Background: Evidence suggests that genetic variations of exon 1 of mannose-binding lectin 2 (MBL2) may contribute to tuberculosis (TB) risk. Many studies have investigated the association between MBL2 exon 1 polymorphisms (rs1800450, rs1800451, and rs5030737) and TB risk, but yielded inconclusive results.

Method: We conducted this meta-analysis of 26 eligible case-control studies that included 7952 cases and 9328 controls to identify the strength of association. Odds ratio (OR) and 95% CI were used to evaluate the strength of association. Statistical analyses were performed by using STATA 12.1.

Results: We found a statistically significant correlation between MBL2 exon 1 polymorphisms and increased TB risk among three models: allele model (O vs A: OR =1.18, 95% CI: 1.01-1.38, P_{heterogeneity}<0.0001, I²=85.8%), homozygote comparison (OO vs AA: OR =1.49, 95%CI: 1.02-2.18, P_{heterogeneity}<0.0001, I²=79.1%), dominant model (AO/OO vs AA: OR =1.20, 95% CI: 1.01-1.43, P_{heterogeneity}<0.0001, I²=83.5%), especially in studies based on Asian populations among five models: allele model (O vs A: OR =1.29, 95% CI: 1.11-1.51, P_{heterogeneity}<0.0001, I²=66.0%), homozygote comparison (OO vs AA: OR =1.67, 95% CI: 1.09-2.55, P_{heterogeneity}=0.008, I²=54.2%), heterozygote comparison (AO vs AA: OR =1.26, 95% CI: 1.05-1.50, P_{heterogeneity}=0.001, I²=62.9%), dominant model (AO/OO vs. AA: OR =1.31, 95% CI: 1.10-1.56, P_{heterogeneity}=0.001, I²=64.2%), and recessive model (OO vs AO/AA: OR =1.50, 95% CI: 1.01-2.22, P_{heterogeneity}=0.023, I²=48.0%). Meta-regression results revealed that source of controls (p=0.009), but not ethnicity (p=0.687), genotyping method (p=0.231), and sample size (p=0.451) contributed to the source of heterogeneity.

Conclusion: This meta-analysis suggests that MBL2 exon 1 polymorphisms may contribute to TB risk, especially in Asian populations.

Keywords: MBL2; polymorphisms; rs1800450; rs1800451; rs5030737; tuberculosis.

Figure 1

PRISMA flowchart. The flow diagram of included and excluded studies. Abbreviations: MBL2, mannose-binding lectin 2; HWE, Hardy–Weinberg equilibrium.

Figure 2

Meta-analysis for the association between the MBL2 exon 1 polymorphisms and tuberculosis risk. Forest plot of (A) allele model (O vs A) and (B) dominant model (AO/OO vs AA). Note: The arrow indicates that the lower limit values of the 95% CI are too low to be shown in the figure. Abbreviations: MBL2, mannose-binding lectin 2; OR, odds ratio.

Figure 3

Sensitivity analysis on (A) all populations and (B) Asians.

Figure 4

Funnel plot analysis to detect publication bias. Funnel plot analysis of (A) allele model (O vs A) on all populations; (B) dominant model (AO/OO vs AA) on all populations; (C) allele model (O vs A) on Asians; and (D) dominant model (AO/OO vs AA) on Asians. Note: The circles represent the weight of individual study. Abbreviations: SE, standard error; OR, odds ratio.