Effect of CYP3A5 gene polymorphisms on tacrolimus concentration/dosage ratio in adult liver transplant patients.

We examined the influence of the cytochrome P450 3A5 (CYP3A5) genes in both donors and recipients on the concentration-dosage ratio (C/D) of tacrolimus in Chinese liver transplant patients. Fifty-one adult liver transplant patients who received tacrolimus were included in this study. The CYP3A5 polymorphism in donors and recipients was determined at the time of transplantation, and tacrolimus-based immunosuppressive therapy was started based on each patient's genetic constitution. The relationship between the C/D of tacrolimus for 3 months after surgery and the CYP3A5 genotype was analyzed. A stepwise regression model was used to analyze the relationship between C/D of tacrolimus and genotype, time course, age, and liver weight in liver transplant patients. Three months after liver transplantation, C/D was both affected by the CYP3A5 genotype of both the donors and the recipients. The C/D of tacrolimus in patients with the CYP3A5*1 allele or carrying CYP3A5*1 allele in the liver was lower than that in CYP3A5*3/*3 patients with the CYP3A5*3/*3 genotype in the liver (P < 0.01). The CYP3A5*1 genotype in donors as well as in patients both contributes to interindividual variation in the C/D of tacrolimus in adult liver transplantation.

Associations of single nucleotide polymorphisms in the Pygo2 coding sequence with idiopathic oligospermia and azoospermia.

Male infertility is often associated with a decreased sperm count. The Pygo2 gene is expressed in the elongating spermatid during chromatin remodeling; thus impairment in PYGO2 function might lead to spermatogenic arrest, sperm count reduction, and subsequent infertility. The aim of this study was to identify mutations in Pygo2 that might lead to idiopathic oligospermia and azoospermia. DNA was isolated from venous blood from 77 men with normal fertility and 195 men with idiopathic oligospermia or azoospermia. Polymerase chain reaction-sequencing analysis was performed for the three Pygo2 coding regions. Non-synonymous single nucleotide polymorphisms (SNPs) were detected and analyzed using SIFT, Polyphen-2, and Mutation Taster softwares to identify possible changes in protein structure that could affect phenotype. Pygo2 sequencing was successful for 178 patients (30 with mild or moderate oligospermia, 57 with severe oligospermia, and 91 with azoospermia). Three previously reported non-synonymous SNPs were identified in patients with azoospermia or severe oligospermic but not in those with mild or moderate oligozoopermia or normozoospermia. SNPs rs61758740 (M141I) and rs141722381 (N240I) cause the replacement of one hydrophobic or hydrophilic amino acid, respectively, with another, and SNP rs61758741 (K261E) causes the replacement of a basic amino acid with an acidic one. The software predictions demonstrated that SNP rsl41722381 would likely result in disrupted tertiary protein structure and thus could be involved in disease pathogenesis. Overall, this study demonstrated that SNPs in the coding region of Pygo2 might be one of the causative factors in idiopathic oligospermia and azoospermia, resulting in male infertility.

A novel DDX5 gene in the freshwater crayfish Cherax quadricarinatus is highly expressed during ontogenesis and spermatogenesis.

The freshwater crayfish Cherax quadricarinatus, originally from Australia, is an invasive species that is also widely used in aquaculture. DEAD-box helicase family genes are found throughout evolution and encode RNA-binding proteins. The human DDX5 (p68) is important for normal cell growth, differentiation and proliferation. We identified a C. quadricarinatus homolog of DDX5 (Cq-DDX5); the temporal expression of Cq-DDX5 mRNA transcripts was measured during early ontogenesis, during spermatogenesis, during testes development, and during the annual cycle. The Cq-DDX5 cDNA comprises 2258 nucleotides, with an open reading frame of 1569 bp, encoding 522 amino acid residues. The deduced amino acid sequence of Cq-DDX5 has a 53 to 90% similarity to DDX5 of other eukaryotic species. mRNA transcripts of Cq-DDX5 were detected in all tissues, with high levels in the gonads. The DDX5 expression was highest in the nauplii stage, during early ontogenesis and during testes development. In adult testes, transcripts appeared at significantly higher levels in the prespawning and spawning phase than in the post-spawning or regressed phase. Eyestalk ablation resulted in upregulation of Cq-DDX5 in adult male gonads in a time-dependent manner, with a peak at about 12 days. We conclude that the Cq-DDX5 gene plays an important role in early ontogenesis and spermatogenesis, with a crucial reproductive function in germ cell differentiation in these invertebrates.