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BACKGROUND: Partial AZFc deletions related to testis-specific gene families are common mutations of the Y chromosome, but their contribution to spermatogenic impairment is still unresolved, and the risk factors for the formation of the deletions remain unknown. With this in mind, we investigated the possible association between Y chromosome haplogroups and predisposition to partial AZFc deletions and their effect on spermatogenesis in a Chinese population. METHODS: The haplogrouping was carried out using 12 polymorphic loci on the Y chromosome in 269 non-AZFc-deleted controls with an unknown spermatogenic status and 214 men with a partial AZFc deletion defined by the absence of the sequence-tagged site and sequence family variant loss of the DAZ and CDY1 genes. In the latter group, 57 men had normozoospermia and 157 men had azoo/oligozoospermia. Among these, 122 had a de novo partial AZFc deletion. RESULTS: Y haplogroup distribution differed significantly between men with a de novo partial AZFc deletion and the control group, and between men with a specific subtype of the partial AZFc deletions and the control group. Further, partial AZFc deletions gave rise to spermatogenesis impairment in some Y haplogroups. CONCLUSIONS: The findings indicate that some monophyletic Y chromosomes may be associated with predisposition to specific subtypes of partial AZFc deletion and adverse effect on spermatogenesis. Although these deletions were not confirmed with gene dosage analysis, the results suggest that Y chromosome background is an important factor that affects partial AZFc deletion formation and its contribution to spermatogenic failure.

Non-obstructive azoospermia (NOA) is a complex, multifactorial disease. Recent genome-wide association studies (GWAS) have identified eight NOA susceptibility loci at genome-wide significance of P < 5.0 × 10(-8) in Han Chinese from southeastern, northern, and central China. To better understand the role of the variants in conferring NOA risk, we selected four GWAS loci (HLA-DRA rs3129878, PRMT6 rs12097821, SOX5 rs10842262, and PEX10 rs2477686) that were reported before 2014 to investigate their association with NOA and their potential effects on sperm production in 1177 Han males from southwest China, including 545 patients with idiopathic NOA and 632 controls with normozoospermia. The results confirmed that the HLA-DRA rs3129878 was an NOA susceptibility locus in the present population. Along with our data, meta-analyses supported the association of the four GWAS-linked loci with NOA, whereas an additive effect of the four loci on NOA susceptibility was not found. Interestingly, the normozoospermic males with the risk genotypes of rs12097821 and rs3129878 + rs10842262 + rs12097821 were observed to have higher total sperm counts relative to non-risk genotypes, suggesting that the risk alleles of the genetic loci may not be via impairing spermatogenic ability to express susceptibility to NOA. These findings may advance our understanding of the role of the NOA susceptibility loci, although the results need to be confirmed in larger samples.

Background. Autosomal dominant polycystic kidney disease (ADPKD) is a common disease in China. The major gene responsible for ADPKD, PKD1, has been fully characterized and shown to encode an integral membrane protein, polycystin 1, which is thought to be involved in cell–cell and cell–matrix interaction. Until now, 82 mutations of PKD1 gene have been reported in European, American, and Asian populations. However, there has been no report on mutations of the PKD1 gene in a Chinese population. Methods. Eighty Chinese patients in 60 families with ADPKD were screened for mutations in the 3′ region of the PKD1 gene using polymerase chain reaction–single-strand conformation polymorphism (PCR–SSCP) and DNA-sequencing techniques. Results. Three mutations were found. The first mutation is a 12593delA frameshift mutation in exon 45, and the polycystin change is 4129WfsX4197, 107 amino acids shorter than the normal polycystin (4302aa). The second mutation is a 12470InsA frameshift mutation in exon 45, producing 4088DfsX4156, and the predicted protein is 148 amino acids shorter than the normal. The third one is a 11151C→T transition in exon 37 converting Pro3648 to Leu. In addition, nine DNA variants, including IVS44delG, were identified. Conclusions. Three mutations in Chinese ADPKD patients are described and all of them are de novo mutations. Data obtained from mutation analysis also suggests that the mutation rate of the 3′ single-copy region of PKD1 in Chinese ADPKD patients is very low, and there are no mutation hot spots in the PKD1 gene. Mutations found in Chinese ADPKD patients, including nucleotide substitution and minor frameshift, are similar to the findings reported by other researchers. Many mutations of the PKD1 gene probably exist in the duplicated region, promoter region, and the introns of PKD1.