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Genetic Polymorphisms of miR-149 Associated with Susceptibility to Both Pulmonary and Extrapulmonary Tuberculosis
Wei-Wei Chen1, Baoshan Wan1, Ranran Zhang1
11 Department of Clinical Laboratory Medicine, Shanghai Pulmonary Hospital Affiliated to Tongji University School of Medicine, Shanghai, P.R. China.
Abstract:
Single nucleotide polymorphisms (SNPs) within precursor microRNAs (miRNAs) can affect the expression of the miRNAs and may be involved in the pathogenesis of pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB). We investigated the potential associations among four precursor miRNA SNPs (miR-149 A>G, C>T; miR-196a2 C>T; miR-499 C>T) and both PTB and EPTB. The study included 380 PTB patients, 242 EPTB patients, and 606 healthy control (HC) subjects from a Chinese Han population. We determined the miRNA relative expression levels from 10 HCs and 10 tuberculosis (TB) patients by quantitative PCR. We found that the PTB group had a significantly lower miR-149 level (p < 0.05) versus the HCs. The allele and genotype frequencies of the miR-149 SNPs were significantly different between the TB patients and the HC group. The C allele at the rs2292832 and the A allele at the rs71428439 locus were associated with susceptibility to EPTB. The C allele of rs2292832 was associated with an increased risk of EPTB compared with that of HCs (p < 0.01), and the A allele of rs71428439 was protective against EPTB (p < 0.01) and PTB (p < 0.01). We identified genetic polymorphisms in miR-149 that appear to be associated with susceptibility to both PTB and EPTB within a Chinese population.
Insights
Single nucleotide polymorphisms in precursor microRNAs (miRNAs) are linked to tuberculosis. Genetic variations in miR-149 are associated with susceptibility to pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) in a Chinese population.
Area of Science:
- Genetics
- Molecular Biology
- Infectious Diseases
Background:
- Single nucleotide polymorphisms (SNPs) in precursor microRNAs (miRNAs) can alter miRNA expression and influence disease development.
- Tuberculosis (TB), encompassing pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB), remains a significant global health challenge.
- Investigating the genetic basis of TB susceptibility is crucial for understanding pathogenesis and developing targeted interventions.
Purpose of the Study:
- To examine the association between specific precursor miRNA SNPs (miR-149, miR-196a2, miR-499) and susceptibility to PTB and EPTB.
- To determine the relative expression levels of miR-149 in TB patients compared to healthy controls.
- To identify potential genetic markers for TB risk within a Chinese Han population.
Main Methods:
- Genotyping of four precursor miRNA SNPs (miR-149 A>G, C>T; miR-196a2 C>T; miR-499 C>T) in 380 PTB patients, 242 EPTB patients, and 606 healthy controls.
- Quantitative PCR (qPCR) was used to measure relative miR-149 expression levels in 10 healthy controls and 10 TB patients.
- Statistical analysis of allele and genotype frequencies to assess associations with PTB and EPTB.
Main Results:
- The PTB group exhibited significantly lower miR-149 expression levels compared to healthy controls (p < 0.05).
- Significant differences in allele and genotype frequencies of miR-149 SNPs were observed between TB patients and healthy controls.
- Specific miR-149 alleles (C at rs2292832, A at rs71428439) were associated with susceptibility or protection against EPTB and PTB.
Conclusions:
- Genetic polymorphisms within miR-149 are associated with susceptibility to both pulmonary and extrapulmonary tuberculosis.
- The identified miR-149 SNPs may serve as potential genetic markers for predicting TB risk.
- Further research is warranted to elucidate the functional mechanisms underlying the role of miR-149 genetic variations in TB pathogenesis.
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