title: Resequencing of the CCL5 and CCR5 genes and investigation of variants for association with diabetic nephropathy.
abstract: Chemokine (C-C motif) ligand 5 (CCL5) and chemokine (C-C motif) receptor 5 are implicated in the pathogenesis of diabetic nephropathy (DN). We hypothesize that variants in these genes may be associated with DN. The CCL5 and chemokine receptor type 5 (CCR5) genes were resequenced, variants identified (n=58), allele frequencies determined in 46 individuals (92 chromosomes) and efficient haplotype tag single-nucleotide polymorphisms (htSNPs) selected to effectively evaluate the common variation in these genes. One reportedly functional gene variant and eight htSNPs were genotyped in a case-control association study involving Caucasian individuals with type 1 diabetes (267 cases with DN and 442 non-nephropathic diabetic controls). Genotyping was performed using MassARRAY iPLEX, TaqMan, gel electrophoresis and direct capillary sequencing. After correction for multiple testing, there were no statistically significant associations between variants in the CCL5 and CCR5 genes and DN.
authors.affiliation: Nephrology Research Group, Queens University Belfast, Belfast, Northern Ireland, UK.
authors.forename: Kerry A
authors.initials: KA
authors.lastname: Pettigrew
authors.forename: Amy Jayne
authors.initials: AJ
authors.lastname: McKnight
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Patterson
authors.forename: Jill
authors.initials: J
authors.lastname: Kilner
authors.forename: Denise M
authors.initials: DM
authors.lastname: Sadlier
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Maxwell
mesh_terms: D000483:Alleles; D018946:Chemokine CCL5 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D019713:Receptors, CCR5 / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D018946:Chemokine CCL5; D019713:Receptors, CCR5