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Tacrolimus is an immunosuppressive drug widely used in kidney transplantation. Cytochrome P450 3A5 (CYP3A5) protein is involved in tacrolimus metabolism. Single nucleotide polymorphism in the CYP3A5gene (6986A>G) results in alteration in metabolic activity of CYP3A5 protein which eventually affects the tacrolimus concentration. Patients with CYP3A5expresser genotypes (A/A *1/*1 and A/G *1/*3) metabolize tacrolimus more rapidly than CYP3A5nonexpressers (G/G *3/*3). We performed meta-analysis to estimate the effect of CYP3A5polymorphism on the trough concentration–dose ratio (Co/D) and risk of renal allograft rejection with similar post-transplant periods and Asian vs. European populations. Our results showed that the tacrolimus Co/D ratio is significantly lower in CYP3A5 expresser group as compared with nonexpresser in Asian as well as in European populations at any post-transplant period (p< 0.00001). No significant association was found with renal allograft rejection episodes between expressers and nonexpressers in European populations (OR: 1.12; p= 0.47). Interestingly, Asian population (with expresser genotypes) and patients after 3 years post-transplantation (with expresser genotypes) have a higher risk of rejection (OR: 1.62; p< 0.05), (OR: 1.68; p< 0.05), respectively. This could be due to high prevalence of expresser genotypes in Asian population. Few tacrolimus-based studies are identified with long-term graft survival. There is a need to have more studies looking for long-term graft survival in expresser as well as no-expresser groups especially in Asian populations who have high frequency of CYP3A5 functional genotype.

•Renal cell carcinoma (RCC) is the most frequent form of kidney cancer in adults.•We report somatic mutations and promoter hypermethylation in 300 RCC patients.•Our data showed molecular alterations in the VHLgene in 163 (54%) RCC patients.•Somatic mutations were found in only 29% patients as compared to 40–70% worldwide.•We found a low frequency of somatic mutations and high frequency of hypermethylation.

Knobloch syndrome (KNO) is an autosomal recessive disorder characterized by ocular abnormalities (myopia and retinal detachment) and occipital encephalocele. The syndrome is clinically and genetically heterogeneous (KNO1, KNO2). Previously germline mutations in COL18A1 (21q22.3) were detected in some families, but in other kindreds linkage to COL18A1 was excluded. We ascertained a large consanguineous family with high myopia, vitreoretinal degeneration and occipital scalp defect with autosomal recessive mode of inheritance. Due to the overlapping clinical presentation of this family with Knobloch syndrome we propose this phenotype as a type III variant of KS (KNO3). A genome wide linkage study using microsatellite markers at 10–20 cM interval revealed linkage to 17q11.2 with a maximum LOD scores 3.40 (θ = 0.00) for markers D17S1307 and D17S1166. Fine mapping defined a 2.67 cM disease region between D17S1307 and D17S798. Mutation analysis of three candidate genes (UNC119, MYO1D, and RAB11FIP4) within the disease region did not identify any disease‐associated mutation in affected individuals. © 2007 Wiley‐Liss, Inc.