Abstract
BackgroundTuberculosis (TB) is still one of the leading causes of death worldwide. Genetic studies have pointed to the relevance of the NOD2 and CD14 polymorphic alleles in association with the risk of diseases caused by Mycobacterium tuberculosis (Mtb) infection.MethodsA systematic review was performed on PubMed, EMBASE, Scientific Electronic Library Online (SciELO), and Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs) to examine the association between single nucleotide polymorphisms (SNP) and risk of Mtb diseases. Study quality was evaluated using the Newcastle-Ottawa Quality Scale (NOQS), and the linkage disequilibrium was calculated for all SNPs using a webtool (Package LDpop).ResultsThirteen studies matched the selection criteria. Of those, 9 investigated CD14 SNPs, and 6 reported a significant association between the T allele and TT genotypes of the rs2569190 SNP and increased risk of Mtb diseases. The genotype CC was found to be protective against TB disease. Furthermore, in two studies, the CD14 rs2569191 SNP with the G allele was significantly associated with increased risk of Mtb diseases. Four studies reported data uncovering the relationship between NOD2 SNPs and risk of Mtb diseases, with two reporting significant associations of rs1861759 and rs7194886 and higher risk of Mtb diseases in a Chinese Han population. Paradoxically, minor allele carriers (CG or GG) of rs2066842 and rs2066844 NOD2 SNPs were associated with lower risk of Mtb diseases in African Americans.ConclusionsThe CD14 rs2569190 and rs2569191 polymorphisms may influence risk of Mtb diseases depending on the allele. Furthermore, there is significant association between NOD2 SNPs rs1861759 and rs7194886 and augmented risk of Mtb diseases, especially in persons of Chinese ethnicity. The referred polymorphisms of CD14 and NOD2 genes likely play an important role in risk of Mtb diseases and pathology and may be affected by ethnicity.Systematic review registrationCRD42020186523
Highlights
Tuberculosis (TB) is still one of the leading causes of death worldwide
Many studies have reported relationships between single nucleotide polymorphisms (SNP) of immune-related genes and risk of Mycobacterium tuberculosis (Mtb) diseases, such as the association between SNPs in TLR4 [5], TNFA [6], and increased risk of active TB among highly exposed individuals. In addition to these genes, the nucleotide-binding oligomerization Domain-Containing protein 2 (NOD2) and Cluster Differentiation antigen 14 (CD14) genes are frequently studied in this setting, as these genes account for proteins that act in the recognition of mycobacterial molecular patterns and lead to immune activation against Mtb [7, 8]
All of the selected studies adopted the case-control design, in which the case was defined as patients with tuberculosis, whether pulmonary, extrapulmonary, or both, and controls were defined as individuals not infected with Mtb
Summary
Genetic studies have pointed to the relevance of the NOD2 and CD14 polymorphic alleles in association with the risk of diseases caused by Mycobacterium tuberculosis (Mtb) infection. Many studies have reported relationships between SNPs of immune-related genes and risk of Mtb diseases, such as the association between SNPs in TLR4 [5], TNFA [6], and increased risk of active TB among highly exposed individuals. In addition to these genes, the nucleotide-binding oligomerization Domain-Containing protein 2 (NOD2) and Cluster Differentiation antigen 14 (CD14) genes are frequently studied in this setting, as these genes account for proteins that act in the recognition of mycobacterial molecular patterns and lead to immune activation against Mtb [7, 8]. While prior studies reported on the role of NOD2 and CD14, many have disparate results, and often are restricted to certain populations [9]
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