Correlation analysis between SNPs in microRNA-machinery genes and tuberculosis susceptibility in the Chinese Uygur population

Medicine (Baltimore). 2018 Dec;97(52):e13637. doi: 10.1097/MD.0000000000013637.

Abstract

Tuberculosis (TB) is an infectious disease caused by a mycobacterial infection, with high morbidity and mortality worldwide. The pathogenesis of TB is still unclear; however, a growing body of evidence suggests that host genetic factors may play important roles in susceptibility to TB, and different gene polymorphisms in different ethnic and genetic backgrounds may lead to different effects. In view of the above theories, our research group used bioinformatics to screen for 12 single nucleotide polymorphisms (SNPs), including rs1045481, rs1045491, rs2740349, rs10719, rs642321, rs3744741, rs7813, rs3742330, rs3757, rs14035, rs720012, and rs4961280, which are derived from 6 main genes (i.e., GEMIN4, DICER1, DROSHA, DGCR8, AGO2, and RAN) acting in the microRNA-machinery pathway. We then analyzed the correlations between TB patients of Uygur in Xinjiang China and the above SNPs using a case-control study. The results showed that the genotypic distributions of rs720012 (from gene DGCR8) and rs4961280 (from gene AGO2) were not in accordance with the Hardy-Weinberg equilibrium (P < .05), so they were deleted. Subjects carrying the rs3742330 AG/GG genotype, rs1045481 GA genotype, rs1045491 CT genotype, and rs7813 AG genotype, respectively, had an increased risk of TB than individuals carrying rs3742330 AA genotype, rs1045481 GG/AA genotype, rs1045491 CC/TT genotype, and rs7813 AA/GG genotype between different groups. Expression quantitative trait loci analysis found that rs3744741 and rs2740349 from gene GEMIN4 had a regulatory effect, while rs3742330 from gene DICER1 had a reverse regulatory effect. Finally, according to the results of Linkage Disequilibrium between SNPs, the haplotype analysis showed that the haplotype of GCTAC from gene GEMIN4 had statistical differences when compared with active and inactive TB. The current experimental results provide a direction for our future research, and the research team will conduct more in-depth studies on the correlation between miRNA and TB.

MeSH terms

  • Adult
  • Argonaute Proteins / genetics
  • Case-Control Studies
  • China / ethnology
  • DEAD-box RNA Helicases / genetics
  • Ethnicity / genetics
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Haplotypes
  • Humans
  • Linkage Disequilibrium / genetics
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Minor Histocompatibility Antigens / genetics
  • Polymorphism, Single Nucleotide*
  • RNA-Binding Proteins / genetics
  • Ribonuclease III / genetics
  • Ribonucleoproteins, Small Nuclear / genetics
  • Tuberculosis / genetics*
  • ran GTP-Binding Protein / genetics

Substances

  • AGO2 protein, human
  • Argonaute Proteins
  • DGCR8 protein, human
  • GEMIN4 protein, human
  • MicroRNAs
  • Minor Histocompatibility Antigens
  • RAN protein, human
  • RNA-Binding Proteins
  • Ribonucleoproteins, Small Nuclear
  • DICER1 protein, human
  • DROSHA protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases
  • ran GTP-Binding Protein