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Published on: August 12, 2017
The implication of genetic variation in the complement C3 allotypes on the first-year allograft outcome after live
Samah Mohamed Awad1, Mohammed Taha2, Mahmoud Omar3
1Department of Clinical Microbiology and Immunology, National Liver Institute, Menoufia University, Egypt.
Insights
The C3-F allele in liver transplant recipients is linked to acute rejection. While C3-SS genotypes may improve survival, C3-SF and C3-FF genotypes are significantly associated with increased rejection risk.
Area of Science:
- Immunogenetics
- Transplantation Immunology
- Complement System Biology
Background:
- The complement component 3 (C3) is crucial in liver transplantation, with the liver as its primary production site.
- C3 exists in slow (C3-S) and fast (C3-F) electrophoretic forms.
Purpose of the Study:
- To investigate the association between C3 gene single nucleotide variations and the first-year outcomes in living donor liver allograft recipients.
- To determine the prevalence of C3-S and C3-F alleles and their genotypes in relation to acute rejection and graft survival.
Main Methods:
- Amplification Refractory Mutation System Polymerase Chain Reaction (ARMS PCR) was used to genotype C3 in 30 liver allograft recipients.
- Outcomes assessed included acute rejection, graft survival, death, graft loss, infection, and Hepatitis C Virus (HCV) recurrence.
Main Results:
- The C3-F allele was more frequent in recipients experiencing acute rejection compared to C3-S.
- C3-SF and C3-FF genotypes showed a significant 6.25-fold increased risk of acute rejection (OR: 6.25; CI: 1.05-37.07, p < .05).
- C3-SS genotype was associated with increased survival (OR: 0.40), though not significantly (p = .3). No significant associations were found for C3 genotypes with overall survival, death, graft loss, infection, or tacrolimus levels.
Conclusions:
- C3-SF and C3-FF genotypes are significantly associated with acute rejection in liver allograft recipients.
- The C3-F allele is more prevalent than C3-S in patients with acute rejection.
- C3-SS genotype may be linked to improved survival, but further studies are needed to confirm this association.
Background:
The component (C3) of the complement system constitutes a central element in liver transplantation. C3 is produced mainly by the liver and comprises both slow (C3-S), and fast (C3-F) components.
Methods:
The effect of a single nucleotide variation in the C3 gene on the first-year outcome examined by ARMS PCR in 30 recipients of living donor allograft.
Results:
Frequencies of C3-S and C3-F in the Egyptian recipients' population were 67% and 33%. C3-F allele frequency was prevalent than the C3-S allele in recipients who developed acute rejection. The C3-SF and C3-FF genotypes significantly associated with acute rejection with 6.25 times increase in the risk of rejection than C3-SS (OR: 6.25; CI:1.05-37.07, p < .05). C3-SS increases the survival 2.5 times more than C3-SF or C3-FF but without significant association (OR: 0.40, CI: 0.07-2.44, p = .3). C3 genotypes or allotypes had no significant association with the recipient's survival, death, graft loss, infection, or serum levels of tacrolimus (all p > .05). C3-FF and C3-SF genotypes had the highest HCV recurrence rate but without significant association (p > .05).
Conclusion:
In liver allograft recipients, C3-SF and C3-FF genotypes significantly associated with acute rejection with the C3-F allele more prevalent than the C3-S. C3-SS genotype increases survival without significant association.
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