Polat Mert, Şahin Feride İffet, Baskin Esra, Toprak Uğur, Gülleroğlu Kaan Savaş, Haberal Mehmet, Terzi Yunus Kasım
Department of Medical Genetics, Faculty of Medicine, Başkent University, Ankara, Turkiye.
Division of Pediatric Nephrology, Department of Pediatrics, Faculty of Medicine, Başkent University, Ankara, Turkiye.
Turk J Med Sci. 2024 Oct 20;54(6):1286-1294. doi: 10.55730/1300-0144.5911. eCollection 2024.
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.
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.
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.
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.
背景/目的：先天性肾脏和尿路畸形（CAKUT）的特征是胚胎期肾脏发育障碍。信号转导和转录激活因子3（STAT3）是STAT蛋白家族的成员。该蛋白家族成员在各种细胞机制中发挥作用，如胚胎发育早期、肾脏发育和肾脏疾病。本研究旨在确定CAKUT患者中STAT3基因rs1053004、rs744166、rs3816769和rs4796793多态性的频率。
采用聚合酶链反应（PCR）和限制性片段长度多态性方法分析rs744166（c.-1-13666T>C，NM_001369512.1）和rs4796793（c.-1915C>G，NM_001369512.1）这两个多态性中的两个。另外两个多态性，rs1053004（c.*1671C>T，NM_001369512.1）和rs3816769（c.273+314A>G，NM_001369512.1），采用实时PCR熔解曲线分析进行检测。
我们的研究表明，rs1053004单核苷酸多态性中携带TT等位基因的个体患CAKUT的风险是携带CC等位基因个体的1.23倍。rs3816769中携带CC等位基因的个体患CAKUT的风险是携带TT等位基因个体的1.41倍。这些发现提示CAKUT可能存在潜在的遗传易感性。此外，该研究还发现罕见单倍型与CAKUT之间存在显著关联（p = 0.041）。rs744166、rs4796793、rs1053004和rs3816769多态性的CCTC单倍型仅在CAKUT组中出现，而相同多态性的CGTT单倍型仅在对照组中检测到。
rs1053004、rs3816769、rs4796793和rs744166多态性的罕见单倍型的存在可能会显著影响CAKUT的发病或预防。这些发现可能具有重要的临床意义，有助于更深入地了解CAKUT的遗传基础，并可能影响未来的诊断和治疗策略。
