A common variant of the PAX2 gene is associated with reduced newborn kidney size.
Congenital nephron number ranges widely in the human population. Suboptimal nephron number may be associated with increased risk for essential hypertension and susceptibility to renal injury, but the factors that set nephron number during kidney development are unknown. In renal-coloboma syndrome, renal hypoplasia and reduced nephron number are due to heterozygous mutations of the PAX2 gene. This study tested for an association between a common haplotype of the PAX2 gene and subtle renal hypoplasia in normal newborns. A PAX2 haplotype was identified to occur in 18.5% of the newborn cohort, which was significantly associated with a 10% reduction in newborn kidney volume adjusted for body surface area. This haplotype was also associated with reduced allele-specific PAX2 mRNA level in a human renal cell carcinoma cell line. Subtle renal hypoplasia in normal newborns may be partially due to a common variant of the PAX2 gene that reduces mRNA expression during kidney development.
Quinlan
Jacklyn
J
Montreal Children's Hospital Research Institute, 4060 Saint Catherine West, PT-413, Montreal, Quebec, Canada.
Lemire
Mathieu
M
Hudson
Thomas
T
Qu
Huiqi
H
Benjamin
Alice
A
Roy
Anne
A
Pascuet
Elena
E
Goodyer
Meigan
M
Raju
Chandhana
C
Zhang
Zhao
Z
Houghton
Fiona
F
Goodyer
Paul
P
D000483:Alleles; D005260:Female; D018507:Gene Expression Regulation, Developmental; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D007231:Infant, Newborn; D007668:Kidney / Q000002:abnormalities* / Q000473:pathology* / Q000502:physiology; D015810:Linkage Disequilibrium; D008297:Male; D009929:Organ Size; D051762:PAX2 Transcription Factor / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism
D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; D012333:RNA, Messenger