Abstract
Background MicroRNA (miRNA) processing machinery gene variant was associated with several diseases. We aimed to explore for the first time the association of machinery gene (DROSHArs10719A/G;DICER1rs3742330A/G;RANrs14035C/T; andXPO5rs11077T/G) variants with the susceptibility and phenotype of end-stage renal disease (ESRD). Method A total of 281 participants (98 ESRD patients and 183 healthy volunteers) were enrolled. Real-Time TaqMan allelic discrimination assay was applied for the genotyping of the specified variants. Multiple logistic regression models, univariate, multivariate, and principal component analyses were carried out. Results Carrying oneDICER1rs3742330*G allele conferred protection against developing ESRD [heterozygote comparison: OR = 0.30, 95% CI = 0.15-0.62, dominant model: OR = 0.35, 95% CI = 0.17-0.70]. Similarly, forXPO5rs11077T/G, homozygote and heterozygote carriers of G variant were less likely to develop ESRD [homozygote comparison: adjusted OR = 0.23, 95% CI = 0.11-0.50, and heterozygote comparison: OR = 0.50, 95% CI = 0.22-0.92, and allelic model: OR = 0.46, 95% CI = 0.34-0.70].RANrs14035*TT subjects were 5 times more likely to develop ESRD while being heterozygote (CT) have twice the risk [homozygote comparison: 5.18, 95% CI = 2.28-11.8, heterozygote comparison: OR = 2.12, 95% CI = 1.10-409]. Subgroup analysis also detectedDICER1rs3742330*A,XPO5rs11077*T, andRANrs14035*T as genetic risk determinants for ESRD development in both sex and age categories. Two genotype combinations ofDROSHA/DICER1/XPO5/RANwere associated with increased susceptibility to ESRD [A-A-T-T: OR = 9.49, 95%CI = 2.48-36.31 (P = .001) and G-A-T-T: OR = 5.92, 95%CI = 1.77-19.83 (P = .004), respectively]. Conclusion Variants and combined genotypes ofDICER1rs3742330,XPO5rs11077, andRANrs14035 might be associated with ESRD development in the study population. Integrating molecular analysis in ESRD risk stratification is warranted.