The Influence of Single Nucleotide Polymorphisms of NOD2 or CD14 on Susceptibility to Tuberculosis: A Systematic Review

Background: Tuberculosis (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 susceptibility or resistance to TB. Methods: A systematic review was performed on search platforms to examine the association between single nucleotide polymorphisms (SNP) and TB risk. Study quality was evaluated using the Newcastle-Ottawa Quality Scale (NOQS) Results: Thirteen 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 TB risk. In contrast, the genotype CC was found to be protective against the disease. Furthermore, in two studies, rs2569191 SNP of the CD14, G allele was described to be significantly associated with increased TB risk. Four studies reported data uncovering the relationship between NOD2 SNPs and TB risk, with two of them reporting significant associations of rs1861759 and rs7194886 and higher TB risk in a Chinese Han population. Paradoxically, minor allele carriers (CG or GG) of rs2066842 and rs2066844 NOD2 SNPs were associated with lower TB risk in African Americans. Conclusions: The CD14 rs2569190 and rs2569191 polymorphisms influence TB risk depending on the allele. Furthermore, there is significant association between NOD2 SNPs rs1861759 and rs7194886 and augmented risk of TB, especially in persons with Chinese ethnicity. The referred polymorphisms of CD14 and NOD2 genes likely play an important role in TB susceptibility and physiopathology; such effect may be affected by ethnicity.Systematic review registration: CRD42020186523