title: Common variants of the glial cell-derived neurotrophic factor gene do not influence kidney size of the healthy newborn.
abstract: Glial cell-derived neurotrophic factor (GDNF) plays an important role in renal development, serving as a trophic factor for outgrowth of the ureteric bud and its continued arborisation. Our previous studies have shown that common variants of the human paired-box 2 (PAX2) gene (a transcriptional activator of GDNF) and rearranged during transfection (RET) gene (encoding the cognate receptor for GDNF) are associated with a subtle reduction in the kidney size of newborns. Since heterozygosity for a mutant GDNF allele causes mild renal hypoplasia and modest hypertension in mice, we considered the possibility that common variants of the GDNF gene might also contribute to renal hypoplasia in humans. We studied the relationship between newborn renal size or umbilical cord cystatin C and 19 common GDNF gene variants [minor allele frequency (MAF) >5%], three single nucleotide polymorphisms (SNPs) related to a putative PAX binding site and one rare SNP (rs36119840 A/G) which changes an amino acid (R93W), based on data from the haplotype map of the human genome (HapMap). However, none of these 23 SNPs was associated with reduced newborn kidney size or function. Among the 163 Caucasians in our cohort, none had the R93W allele.
authors.affiliation: McGill University Montreal Children's Hospital Research Institute, Montreal, QC, Canada.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jackie
authors.initials: J
authors.lastname: Quinlan
authors.forename: David
authors.initials: D
authors.lastname: Grote
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lemire
authors.forename: Thomas
authors.initials: T
authors.lastname: Hudson
authors.forename: Alice
authors.initials: A
authors.lastname: Benjamin
authors.forename: Anne
authors.initials: A
authors.lastname: Roy
authors.forename: Elena
authors.initials: E
authors.lastname: Pascuet
authors.forename: Meigan
authors.initials: M
authors.lastname: Goodyer
authors.forename: Chandhana
authors.initials: C
authors.lastname: Raju
authors.forename: Fiona
authors.initials: F
authors.lastname: Houghton
authors.forename: Maxime
authors.initials: M
authors.lastname: Bouchard
authors.forename: Paul
authors.initials: P
authors.lastname: Goodyer
mesh_terms: D000483:Alleles; D015331:Cohort Studies; D055316:Cystatin C / Q000097:blood; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D005787:Gene Frequency; D014644:Genetic Variation; D015894:Genome, Human; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007231:Infant, Newborn; D007668:Kidney / Q000254:growth & development* / Q000378:metabolism; D015810:Linkage Disequilibrium; D008297:Male; D009399:Nephrons / Q000254:growth & development; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D044465:White People / Q000235:genetics
chemical_list: D055316:Cystatin C; D051100:Glial Cell Line-Derived Neurotrophic Factor; D012333:RNA, Messenger