A Notch4 missense mutation is associated with susceptibility to tuberculosis in Chinese population.

Abstract

BACKGROUND:

The infection process of tuberculosis is related to the interactions between Mycobacterium tuberculosis (MTB) and the host immune system. Polymorphisms in genes involved in the host immune system are related to susceptibility to tuberculosis. The Notch signalling pathway regulates innate and adaptive immunity. Notch4 is a member of the Notch receptor family and may be a negative regulator of Mtb-induced inflammation. However, little is known about the association between Notch4 genetic polymorphisms and susceptibility to tuberculosis; therefore, we explored the association between Notch4 variants and susceptibility to tuberculosis in China.

MATERIALS AND METHODS:

A total of 900 tuberculosis patients and 1534 healthy people serving as controls were enrolled consecutively at West China Hospital between January 2014 and February 2016 Twelve selected SNPs (rs2071277, rs2071285, rs206016, rs438475, rs2256594, rs429853, rs422951, rs415929, rs915895, rs443198, rs3830041 and rs375244) were genotyped by a custom-by-design 2 48-plex SNP scan TM kit. The frequencies of the alleles, genotypes and genetic models of the variants were compared between the two groups, while the SNP-SNP interactions were analysed by Multifactor Dimensionality Reduction (MDR) software. The odds ratio (OR) with a corresponding 95% confidence interval (CI) was calculated.

RESULTS:

The G allele rs2071277 of Notch4 was associated with a decreased risk for tuberculosis (OR 0.844; 95% CI 0.748-0.954, p = .006). The G allele rs422951 of Notch4 was associated with a decreased risk for tuberculosis (OR 0.818; 95% CI 0.703-0.950, p = .008). These findings were consistent with the results from both the dominant model and additive model. The allele, genotype and genetic model frequencies for the other SNPs were similar in the two groups (all P > .05). One haplotype (GTG) consisting of rs2071277, rs2071285 and rs206016 was associated with tuberculosis risk (p = .011).

CONCLUSION:

Ours is the first study implies that the G allele variants of rs2071277 and rs422951 in Notch4 influence susceptibility to tuberculosis in a Chinese population, suggesting that Notch signalling is involved in the pathogenesis of tuberculosis. More studies with functional verification will refine our understanding of the role of Notch signalling and provide novel avenues for therapeutic intervention.

• Authors: Jingwei Zhang, Lin Jiao, Hao Bai, Qian Wu, Tao Wu, Tangyuheng Liu, Xuejiao Hu, Jiajia Song, Binwu Ying
• Journal: Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases (Infect Genet Evol) Vol. 78 Pg. 104145 (03 2020) ISSN: 1567-7257 [Electronic] Netherlands
• PMID: 31838262 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019. Published by Elsevier B.V.

Chemical References

• NOTCH4 protein, human
• Receptor, Notch4
• Notch4 protein, mouse

Topics

• Adult
• Animals
• Asian People (genetics)
• Case-Control Studies
• Female
• Genetic Predisposition to Disease
• Haplotypes
• Humans
• Male
• Mice
• Middle Aged
• Mutation, Missense
• Polymorphism, Single Nucleotide
• Receptor, Notch4 (genetics)
• Tuberculosis (genetics)