Association of TP53 Germline Variant and Choledochal Cyst among Clinically Diagnosed Filipino Pediatric Patients
Danna Mae S Opiso1, Germana Emerita V Gregorio2, Catherine Lynn T Silao2,3
1College of Medicine, University of the Philippines Manila.
Insights
This study found no association between the TP53 rs201753350 variant and choledochal cysts in Filipino children. Further research is recommended to explore other genetic factors in choledochal cyst development.
Area of Science:
- Genetics
- Pediatric Gastroenterology
- Oncology
Background:
- Choledochal cysts (CC) are rare congenital biliary dilations more common in Asian females and children.
- Symptoms include abdominal pain, mass, and jaundice, suggesting a potential genetic basis.
- The TP53 gene's germline variant rs201753350 (c.91G>A) may influence cell proliferation and is investigated here.
Purpose of the Study:
- To determine the prevalence of the TP53 rs201753350 germline variant in Filipino pediatric patients.
- To investigate the association between this variant and the occurrence of choledochal cysts in this population.
Main Methods:
- Genomic DNA was extracted from blood samples of pediatric choledochal cyst cases and controls.
- Polymerase chain reaction (PCR), electrophoresis, and sequencing were used for analysis.
Main Results:
- The study included 109 participants (22 cases, 87 controls).
- The A allele (22.94%) and G allele (77.06%) frequencies were similar in cases and controls.
- No significant association was found between the rs201753350 variant (A allele or A/G genotype) and choledochal cyst occurrence.
Conclusions:
- The TP53 rs201753350 germline variant is not significantly associated with choledochal cysts in Filipino children.
- Future studies should explore other TP53 mutations and genes for potential links to choledochal cyst development.
Background And Objective:
Choledochal cysts (CC) are rare congenital, cystic dilations of the biliary tree occurring predominantly in Asian populations and in females. Patients are usually children presenting with any of the following: abdominal pain, palpable abdominal mass, and jaundice. Its congenital nature hints at a potential genetic cause. A possible causal gene is TP53, a tumor suppressor with a germline variant called rs201753350 (c.91G>A) that changed from a G allele to an A allele, decreasing the cell proliferation suppressing activity of its functional protein. Currently, there is no information on the TP53 rs201753350 germline variant available for the Filipino population. This study determined the prevalence of rs201753350 and the association between the functional G allele, the rs201753350 germline variant A allele, and the occurrence of CCs in Filipino pediatric patients in a tertiary government hospital.
Methods:
Genomic DNA was extracted from blood samples of pediatric patients clinically diagnosed with CC. Controls were DNA samples collected from a previous study. The samples underwent PCR, electrophoresis, and sequencing.
Results:
A total of 109 participants (22 cases and 87 controls) were included in the study. The A allele (22.94%) occurs at a lower frequency than the G allele (77.06%) among both cases and controls. More individuals have a homozygous G/G genotype (54.13%) than a heterozygous A/G genotype (45.87%) while the homozygous A/A genotype was not observed. The estimated risk of choledochal cyst occurrence is significantly lower in individuals with the A allele (PR: 0.08, 95% CI: 0.01 - 0.55) and the A/G genotype (PR: 0.06, 95% CI: 0.01 - 0.40).
Conclusion:
There is no significant evidence to suggest an association between the TP53 rs201753350 germline variant and the occurrence of choledochal cysts in Filipinos. It is recommended that other mutations within and beyond the TP53 gene be investigated for possible associations with choledochal cyst occurrence.
Related Concept Videos
01:23Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
01:26Endoscopic Procedures V: ERCP
Patient...