title: Resequencing of the characterised CTGF gene to identify novel or known variants, and analysis of their association with diabetic nephropathy.
abstract: Connective tissue growth factor (CTGF) has been implicated in the pathogenesis of diabetic nephropathy; however, to date there have been no reports of genomic analysis on this gene. The CTGF gene was comprehensively screened using WAVE (dHPLC) technology and direct capillary sequencing. Single nucleotide polymorphisms (SNPs) with minor allele frequencies greater than 5% were further investigated in an Irish, type 1 diabetic population. The case-control collection consisted of 272 diabetics with nephropathy and 367 non-nephropathic diabetic controls who were genotyped using TaqMan and Pyrosequencing technologies. Ten SNPs were identified, of which seven were novel. Four SNPs are located in the promoter, one in exon 2, two in intron 2 and three in the 3' untranslated region. Based on in silico analysis, three SNPs, c.-650G>C, c.-484T>C and c.247G>C, are potentially functional. Subsequent statistical analysis for common SNPs, c.-650G>C, c.-420InsT, c.-220G>C, c.289+94T>C and c.289+98T>C, in the case-control study revealed no significant differences in genotype or allele frequencies. CTGF has emerged as a biological candidate gene for diabetic nephropathy; however, no significant association was detected between common CTGF SNPs and nephropathy in this population.
authors.affiliation: Nephrology Research Group, Queen's University of Belfast, c/o Regional Genetics Centre, Level A, Tower Block, Belfast City Hospital, Lisburn Road, BT9 7AB, Belfast, Northern Ireland. a.j.mcknight@qub.ac.uk.
authors.forename: Amy Jayne
authors.initials: AJ
authors.lastname: McKnight
authors.affiliation: Nephrology Research Group, Queen's University of Belfast, c/o Regional Genetics Centre, Level A, Tower Block, Belfast City Hospital, Lisburn Road, BT9 7AB, Belfast, Northern Ireland.
authors.forename: David A
authors.initials: DA
authors.lastname: Savage
authors.affiliation: Department of Epidemiology and Public Health, Queen's University of Belfast, Belfast, Northern Ireland.
authors.forename: Chris C
authors.initials: CC
authors.lastname: Patterson
authors.affiliation: Dublin Molecular Medicine Centre, Conway Institute, Dublin, Ireland.
authors.forename: Hugh R
authors.initials: HR
authors.lastname: Brady
authors.affiliation: Nephrology Research Group, Queen's University of Belfast, c/o Regional Genetics Centre, Level A, Tower Block, Belfast City Hospital, Lisburn Road, BT9 7AB, Belfast, Northern Ireland.
authors.forename: A Peter
authors.initials: AP
authors.lastname: Maxwell
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002648:Child; D002896:Chromosomes, Human, Pair 6; D055513:Connective Tissue Growth Factor; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics; D017422:Sequence Analysis, DNA; D044465:White People / Q000235:genetics
chemical_list: C526317:CCN2 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D055513:Connective Tissue Growth Factor