With the development of genome-wide association studies, millions of mutations have been discovered, most of which are single nucleotide substitutions . These mutations are also referred to as SNPs. SNPs can occur in any region of the genome which is likely due to various selection pressures that generate single-base mutations in specific regions of the genome, with varying frequencies . There are two types of SNPs, namely synonymous and non-synonymous SNPs. Synonymous SNPs do not alter encoded amino acids, whereas non-synonymous SNPs do alter amino acids and may ultimately influence certain protein properties or functions. Additionally, studies have found that non-synonymous SNPs may also play a regulatory role by interacting with non-coding RNAs .
To date, more than 15,000 SNPs of the BAFF gene have been identified, yet fewer than 20 of these SNPs have been intensively studied. In this present study, five BAFF/BAFF-R SNPs were selected, including three BAFF SNPs located in the promoter region and two non-synonymous BAFF-R SNPs. Considering the role of BAFF/BAFF-R signaling in antibody-mediated rejection, the primary purpose of this study was to analyze the correlation between these five SNPs and chronic rejection in kidney transplant recipients. Since the number of pathologically confirmed patients presenting with chronic rejection was limited, we used eGFR as an indicator of graft renal function during the data analyses.
Ultimately, we found that having the BAFF rs9514828 CT genotype may be a risk factor for Han Chinese from the Jiangsu Province, resulting in reduced renal allograft function after kidney transplantation, however, no significant correlation with sBAFF or positive rate of PRA was found. Gottenberg et al.  studied 162 French patients with Sjogren’s syndrome and found that patients with the rs9514828 TT genotype had higher levels of sBAFF, which was associated with anti-SSA and anti-SSB antibody levels. Furthermore, Kawasaki et al.  studied Japanese patients with SLE and rheumatoid arthritis and found that rs9514828 TT genotype carriers tended to have higher levels of anti-Sm antibodies, and patients with the -871 T allele had significantly higher levels of BAFF mRNA in monocytes. However, several studies related to rs9514828 have not obtained significant results [18,19]. Kompoti et al.  found that severely ill patients with the rs61756766 C allele had a lower risk of acquiring sepsis in the ICU, but no association was found between rs61756766 and susceptibility to sepsis in trauma and surgical patients in Greece. In a study of Spanish patients with immunoglobulin A vasculitis, BAFF, APRIL, and BAFF-R SNPs, including BAFF-R rs77874543, were not found to be associated with the pathological mechanisms of the disease . We also examined two non-synonymous BAFF-R SNPs, but did not obtain statistically significant results. We postulate that the different significant genotype results found in these studies may be due to variation in pathological mechanisms or ethnic differences.
The analyses of clinical data for significantly differentiated genotypes in this present study included assessing the association between sBAFF and positive rate of PRA, however, no significant results were obtained.
Currently, only two reports related to BAFF SNPs and kidney transplantation have been published on PubMed. One study assessed Hispanic white kidney transplant recipients and found that BAFF rs12583006 was associated with a higher level of the class II donor specific antibody . The other study investigated BAFF system SNPs (including BAFF, three BAFF receptor SNPs, and APRIL SNPs) in Hispanic white kidney transplant recipients, and found that the APRIL rs3803800 AA genotype may be high risk factor for acute rejection. Compared to GG/GA carriers, recipients with this genotype had a significant acute rejection free time . Interestingly, despite both studies investigating kidney transplant recipients, contrasting results were found. This begs the question: are these different findings related to geographical, or ethnic differences? Ultimately, more data needs to be gathered before drawing such conclusions.
Graft renal function is affected by several factors, and immune rejection caused by alloantigens should be one of the important ones , and some evidences suggested that the rate of graft loss caused by antibody-mediated rejection is more than 50% . The successful development of novel immunosuppressants has many benefits for transplant recipients. Belimumab, a specific anti-BAFF monoclonal antibody, has been approved by the US Food and Drug Administration for the treatment of SLE, however, unexpected effects have been observed in some patients . Moreover, belimumab did not meet certain clinical expectations in a phase II trial in kidney transplant recipients . Some studies suggest that differences in belimumab efficacy may be due to individual genetic factors . Ultimately, further research is required to determine whether BAFF SNPs affect the action of BAFF-specific antibody reagents.
Kidney transplant recipients with the GCG haplotype may be prone to abnormal graft function. Indeed, all clinical indices of recipients with the rs16972194 and rs16972197 SNPs were coincident (for all seven kidney transplant recipients). This finding is consistent with the linkage disequilibrium analysis results and our initial hypotheses.
At present, research methods concerning SNPs have seen an increase in quantity and ease of use, resulting in an improved understanding of SNPs. Remarkable strides in SNP research have taken place since the construction of an SNP database , completion of protocols for a genome-wide, preponderant SNP network , and development of a model to predict tacrolimus levels in pediatric solid organ transplant recipients, by integrating clinical data with genetic factors . The effect of the interaction between different SNPs, and between SNPs and non-coding RNAs (such as miRNA and lncRNA) on the translation, expression, and function of relevant genes forms an important component of SNP research [32,33].
SNPs represent stable genetic alterations in the genome . The present study partially elucidated the correlation between genomic SNPs found in kidney transplant recipients in the Jiangsu Province. We aim to increase the sample size and screen for BAFF SNPs related to chronic rejection, and combine this informaion with the pathological diagnosis. Ultimately, this work will help to establish individual treatment protocols after kidney transplantations to obtain satisfactory long-term outcomes based on genetic variation.