Rare STAT3 haplotypes cause a predisposition to developing congenital anomalies of the kidney and urinary tract disorder.

Background/aim: Congenital anomalies of the kidney and urinary tract (CAKUT) are characterized by renal developmental disorders in the embryonic period. STAT3 is a member of the STAT protein family. The members of this protein family play roles in various cellular mechanisms, such as the early stages of embryonic development, kidney development, and renal diseases. This study aims to determine the frequency of STAT3 rs1053004, rs744166, rs3816769, and rs4796793 polymorphisms in individuals with CAKUT.

Materials and methods: Two of four polymorphisms, rs744166 (c.-1-13666T>C, NM_001369512.1) and rs4796793 ( c.-1915C>G, NM_001369512.1), were analyzed by a polymerase chain reaction (PCR) and the restriction fragment length polymorphism method. Two other polymorphisms, rs1053004 (c.*1671C>T, NM_001369512.1) and rs3816769 (c.273+314A>G, NM_001369512.1), were analyzed using real-time PCR-melting curve analysis.

Results: Our research indicates that individuals with the TT allele for rs1053004 single nucleotide polymorphism have a 1.23 times greater disease risk than those with the CC allele. Those with the CC allele for rs3816769 have a 1.41 times greater risk of disease than those with the TT allele. These findings suggest a potential genetic predisposition to CAKUT. Furthermore, the research identified significant connections between rare haplotypes and CAKUT (p = 0.041). The CCTC haplotype for rs744166, rs4796793, rs1053004, and rs3816769 polymorphism was exclusively present in the CAKUT group, while the CGTT haplotype for the same polymorphisms was only detected in the control group.

Conclusion: The presence of rare haplotypes for the rs1053004, rs3816769, rs4796793, and rs744166 polymorphisms may significantly affect the onset or prevention of CAKUT. These findings could potentially have important clinical implications, providing a deeper understanding of the genetic basis of CAKUT and potentially influencing future diagnostic and treatment strategies.