title: Ameliorative effects of SLC22A2 gene polymorphism 808 G/T and cimetidine on cisplatin-induced nephrotoxicity in Chinese cancer patients.
abstract: To investigate the roles of SLC22A2 gene polymorphism 808 G/T and cimetidine on cisplatin-induced nephrotoxicity, a total of 123 Chinese cancer patients treated with cisplatin alone (n = 55) or in combination with cimetidine (n = 68) were genotyped. The changes of serum creatinine (SCr), blood urea nitrogen (BUN) and cystatin C levels were used as biomarkers for the evaluation of cisplatin-induced nephrotoxicity. The changes of BUN and SCr levels showed no significant difference between groups divided by genotypes and treatments (P > 0.05). However, patients with mutant genotype (GT/TT) or with cimetidine treatment had smaller increase of the cystatin C levels compared to those with wild genotype (GG) or without cimetidine treatment (P < 0.05). In the non-cimetidine-treated group, the changes of cystatin C level in patients with mutant genotype (GT/TT) was significantly smaller than those with wild genotype (GG) (P = 0.043). In the wild type group, the cystatin C level change of patients without cimetidine treatment was significantly larger than those with cimetidine treatment (P = 0.007). These results suggested that SLC22A2 gene polymorphism 808 G/T and cimetidine could attenuate cisplatin nephrotoxicity in Chinese cancer patients. But the renoprotection mechanism of cimetidine might be damaged by the mutation.
authors.affiliation: Department of Pharmacy, School of Pharmaceutical Sciences, Shandong University, 44 Wenhua West Road, Jinan 250012, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Wen
authors.initials: W
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001483:Base Sequence; D001806:Blood Urea Nitrogen; D002681:China; D002927:Cimetidine / Q000627:therapeutic use*; D002945:Cisplatin / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D055316:Cystatin C / Q000097:blood; D017931:DNA Primers; D005260:Female; D005838:Genotype; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D000075102:Organic Cation Transporter 2; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
chemical_list: D000970:Antineoplastic Agents; D055316:Cystatin C; D017931:DNA Primers; D027701:Organic Cation Transport Proteins; D000075102:Organic Cation Transporter 2; C491013:SLC22A2 protein, human; D002927:Cimetidine; D003404:Creatinine; D002945:Cisplatin