Common variants of the glial cell-derived neurotrophic factor gene do not influence kidney size of the healthy newborn

Pediatr Nephrol. 2009 Jun;24(6):1151-7. doi: 10.1007/s00467-008-1097-2. Epub 2009 Jan 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Cohort Studies
  • Cystatin C / blood
  • European Continental Ancestry Group / genetics
  • Female
  • Fetal Blood / chemistry
  • Gene Frequency
  • Genetic Variation*
  • Genome, Human
  • Glial Cell Line-Derived Neurotrophic Factor / genetics*
  • Haplotypes
  • Humans
  • Infant, Newborn
  • Kidney / growth & development*
  • Kidney / metabolism
  • Linkage Disequilibrium
  • Male
  • Nephrons / growth & development
  • Organ Size
  • Polymorphism, Single Nucleotide
  • RNA, Messenger / metabolism


  • Cystatin C
  • Glial Cell Line-Derived Neurotrophic Factor
  • RNA, Messenger