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Objective: To investigate the association between genetic variants in the major histocompatibility complex (MHC) region and nonobstructive azoospermia (NOA) susceptibility.Design: MHC region fine-mapping analysis based on previous NOA genome-wide association study (GWAS) data.Setting: Medical university.Patient(s): Nine hundred and eighty-one men with NOA and 1,657 normal fertile male controls.Intervention(s): None.Main Outcome Measure(s): The MHC region imputation assessed with SNP2HLA software, taking the specific Han-MHC database as a reference panel; statistical significance of the MHC variants calculated using logistic regression models; functional annotation based on online public databases; and phenotypic variances explained by specific groups of genetic variants estimated using the fixed effects model from individual associations.Result(s): Two independent risk loci, rs7194 (odds ratio [OR] 1.37) at MHC class II molecules and rs4997052 (OR 1.30) at MHC class I molecules, were identified. Functional annotation showed rs7194 may tag the effect of multiple amino acid residues and the expression of HLA-DQB1 and HLA-DRB1; while rs4997052 showed the effect of amino acid changes of HLA-B at position 116 as well as the expression of HLA-B and CCHCR1, which coexpressed with genes enriched in pathways of spermatogenesis and male gamete generation. The novel variant rs4997052 identified in our study can explain another approximately 0.66% of the phenotypic variances of NOA.Conclusion(s): We fine-mapped the MHC region and identified two loci that independently drove NOA susceptibility. These results provide a deeper understanding of the association mechanisms of MHC and NOA risk. [ABSTRACT FROM AUTHOR]

Abstract: MicroRNAs (miRNAs) can act as oncogenes or tumor-suppressor genes in human cancers including HCC. Previous studies have identified miR-34 family as an important component of the tumor suppressor network during carcinogenesis. In this study, we investigated the methylation status of miR-34 family in HCC tumor and adjacent non-tumor tissues using methylation-specific PCR (MSP). The methylation frequencies of miR-34a and miR-34b/c were 72.1% (31/43) and 79.1% (34/43) in HCC tissues, which were significantly higher than that in the adjacent non-tumor tissues (P <0.05), respectively. The results were validated by bisulfite sequencing PCR (BSP). Quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis showed that the expression of miR-34a and miR-34b was significantly down-regulated in HCC tissues compared with adjacent non-tumor tissues (P <0.05). Moreover, the expression of miR-34b was inversely correlated to CpG island methylation in tumor tissues, but not for miR-34a. In summary, our results suggest that DNA methylation may be involved in the inactivation of miR-34b in HCC. [Copyright &y& Elsevier]