A common RET variant is associated with reduced newborn kidney size and function

Area of Science:

• Genetics
• Nephrology
• Developmental Biology

Background:

• Congenital nephron number varies significantly among individuals.
• Lower nephron counts are associated with increased risk for hypertension and renal insufficiency.
• Mechanisms determining nephron number are not fully understood.

Purpose of the Study:

• To investigate the hypothesis that common variants of the RET gene influence congenital nephron number.
• To explore the role of RET gene variants in subtle renal hypoplasia in newborns.

Main Methods:

• Identification of a single-nucleotide polymorphism (rs1800860 G/A) in exon 7 of the RET gene.
• Analysis of the functional impact of the adenosine variant (1476A) on mRNA splicing and transcript levels in human cells.
• In vivo assessment of kidney volume and cord blood cystatin C levels in newborns with different rs1800860 genotypes.

Main Results:

• The rs1800860(1476A) allele was associated with reduced affinity for spliceosome proteins and increased aberrant mRNA splicing.
• Newborns with the rs1800860(1476A) allele exhibited 10% smaller kidney volumes.
• Newborns with the rs1800860(1476A) allele had 9% higher cord blood cystatin C levels.

Conclusions:

• A common RET gene variant (rs1800860(1476A)) may contribute to subtle renal hypoplasia in a proportion of the white population.
• This genetic variation could influence kidney development and potentially impact long-term clinical outcomes.
• Further research is needed to determine the clinical significance of this gene variant on health outcomes.