Identification of Single-Nucleotide Polymorphisms Associated with Renal Dysfunction After Lung Transplantation Using Ethnic-Specific SNP Array

Abstract

<h3>Purpose</h3> Renal dysfunction is a well-known long-term complication that could increase mortality after lung transplantation (LT). The proportion of severe renal dysfunction increases overtime to reach 24.6% within 10 years after LT. The development of severe renal dysfunction has been shown to be associated with increased mortality after LT. However, the association between single-nucleotide polymorphism (SNP) and renal dysfunction after LT has not been elucidated. In this study, we aimed to investigate SNPs associated with renal dysfunction after LT using the SNP array for the Japanese population, Japonica Array NEO (Toshiba, Japan), comprising a total of 66,883 markers. <h3>Methods</h3> We collected blood samples from 99 recipients after LT. First, among these, 34 qualified samples were genotyped using the SNP array. According to the homozygous and heterozygous mutant alleles of 162 SNPs associated with renal dysfunction, they were divided into two groups. The renal function tests, including creatinine and eGFR, were compared between the two groups in each SNP. Next, after identifying candidate SNPs, we investigated the association between the candidate SNPs and the renal function of all 99 recipients. Delta eGFR (ΔeGFR) was defined as the difference between the postoperative and preoperative baseline levels. <h3>Results</h3> A total of 8 SNPs (rs102275, rs10277115, rs174549, rs2980098, rs4690095, rs72719193, rs792064 and rs7956634) were identified as candidate SNPs associated with renal dysfunction after LT. Validation analysis of these 8 candidate SNPs in all 99 recipients showed that three SNPs (rs10277115, rs4690095, and rs792064) were associated with significant differences in the postoperative change of ΔeGFR after LT (Fig. 1). <h3>Conclusion</h3> Three SNPs, rs10277115, rs4690095 and rs792064, were associated with significant differences in eGFR in the long term and the development of renal dysfunction after LT.