Association of UGT1A Gene Polymorphisms with BKV Infection in Renal Transplantation Recipients

Title:Association of UGT1A Gene Polymorphisms with BKV Infection in Renal Transplantation Recipients

Volume: 25 Issue: 3

Author(s): Jingwen Yuan, Shuang Fei, Zeping Gui, Zijie Wang, Hao Chen, Li Sun, Jun Tao, Zhijian Han, Xiaobing Ju, Ruoyun Tan*, Min Gu*Zhengkai Huang*

Affiliation:

• Department of Urology, The First Affiliated Hospital with Nanjing Medical University, Nanjing. 210029, China

• Department of Urology, The First Affiliated Hospital with Nanjing Medical University, Nanjing. 210029, China
• Department of Urology, The Second Affiliated Hospital with Nanjing Medical University, Nanjing. 210011, China

• Department of Urology, The First Affiliated Hospital with Nanjing Medical University, Nanjing. 210029, China

Abstract:

Background: BK virus (BKV) infection is an opportunistic infectious complication and constitutes a risk factor for premature graft failure in kidney transplantation. Our research aimed to identify associations and assess the impact of single-nucleotide polymorphisms (SNPs) on metabolism-related genes in patients who have undergone kidney transplantation with BKV infection.

Material/Methods: The DNA samples of 200 eligible kidney transplant recipients from our center, meeting the inclusion criteria, have been collected and extracted. Next-generation sequencing was used to genotype SNPs on metabolism-associated genes (CYP3A4/5/7, UGT1A4/7/8/9, UGT2B7). A general linear model (GLM) was used to identify and eliminate confounding factors that may influence the outcome events. Multiple inheritance models and haplotype analyses were utilized to identify variation loci associated with infection caused by BKV and ascertain haplotypes, respectively.

Results: A total of 141 SNPs located on metabolism-related genes were identified. After Hardy-Weinberg equilibrium (HWE) and minor allele frequency (MAF) analysis, 21 tagger SNPs were selected for further association analysis. Based on GLM results, no confounding factor was significant in predicting the incidence of BK polyomavirus-associated infection. Then, multiple inheritance model analyses revealed that the risk of BKV infection was significantly associated with rs3732218 and rs4556969. Finally, we detect significant associations between haplotype T-A-C of block 2 (rs4556969, rs3732218, rs12468274) and infection caused by BKV (P = 0.0004).

Conclusions: We found that genetic variants in the UGT1A gene confer BKV infection susceptibility after kidney transplantation.

Cite this article as:

Yuan Jingwen, Fei Shuang, Gui Zeping, Wang Zijie, Chen Hao, Sun Li, Tao Jun, Han Zhijian, Ju Xiaobing, Tan Ruoyun*, Gu Min*, Huang Zhengkai*, Association of UGT1A Gene Polymorphisms with BKV Infection in Renal Transplantation Recipients, Current Drug Metabolism 2024; 25 (3) . https://dx.doi.org/10.2174/0113892002282727240307072255