RESUMEN
PURPOSE: A genome-wide association study conducted in the Han Chinese population identified three single nucleotide variants rs12097821, rs2477686, and rs10842262 as being significantly associated with non-obstructive azoospermia. Our aim was to evaluate the possible association between these susceptibility loci and idiopathic male infertility risk in the Serbian population. METHODS: A case-control study was conducted on 431 male individuals from the Serbian population divided into two groups. The case group consisted of 208 males diagnosed with oligoasthenozoospermia or non-obstructive azoospermia, while the control group involved 223 fertile men who have fathered at least one child. RESULTS: According to codominant (Pcodom = 0.048, ORcodom = 0.57, 95%CI 0.35-0.92) and overdominant (Poverdom = 0.017, ORoverdom = 0.62, 95%CI 0.42-0.92) genetic models, rs10842262 was found to be associated with male infertility. Stratifying infertile men according to diagnosis yielded statistically significant results for non-obstructive azoospermia cases under multiple genetic models (Pcodom = 0.038, ORcodom = 0.47, 95%CI 0.26-0.85; Pdom = 0.031, ORdom = 0.53, 95%CI 0.30-0.94; Poverdom = 0.016, ORoverdom = 0.55, 95%CI 0.33-0.90). Minor allele C of rs2477686 genetic variant was shown to be associated with the reduced risk of oligoasthenozoospermia under the log-additive genetic model (P = 0.03, OR = 0.69, 95%CI 0.50-0.97). The results of the meta-analysis indicate both rs2477686 and rs10842262 to be associated with male infertility. CONCLUSION: Our results show variants rs2477686 and rs10842262 to be significantly associated with male infertility in the Serbian population. Nevertheless, case-control studies in other populations are needed to validate their association with infertility in males diagnosed with oligoasthenozoospermia and non-obstructive azoospermia.
Asunto(s)
Azoospermia/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Infertilidad Masculina/genética , Adulto , Alelos , Azoospermia/epidemiología , Azoospermia/patología , Estudios de Casos y Controles , Frecuencia de los Genes , Genética de Población , Genotipo , Humanos , Infertilidad Masculina/epidemiología , Infertilidad Masculina/patología , Masculino , Proteínas Nucleares/genética , Peroxinas/genética , Polimorfismo de Nucleótido Simple/genética , Proteína-Arginina N-Metiltransferasas/genética , Receptores Citoplasmáticos y Nucleares/genética , Factores de Transcripción SOXD/genética , Serbia/epidemiologíaRESUMEN
MiR-21 and miR-375 have been reported as dysregulated in prostate cancer (PCa) in multiple previous studies. Still, variable or even opposing data for the expression of these microRNAs in PCa were found, and their potential biomarker properties remain elusive. In an attempt to clarify their significance as PCa biomarkers, as well as to compare different types of specimens as a source of relevant microRNAs, we used plasma and matching plasma-derived exosomes from patients with PCa and patients with benign prostatic hyperplasia (BPH). Plasma and exosomes were obtained from 34 patients with PCa and 34 patients with BPH, and their levels of expression of miR-21 and miR-375 were determined by RT-qPCR. We found no significant difference in the level of expression of these microRNAs in plasma and exosomes between patients with PCa and BPH. The level of exosomal miR-21 was elevated in PCa patients with high serum PSA values, as well as in patients with aggressive PCa, while for plasma samples, the results remained insignificant. For miR-375, we did not find an association with the values of standard prognostic parameters of PCa, nor with cancer aggressiveness. Therefore, our results support the potential prognostic role of exosomal miR-21 expression levels in PCa.