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Associaton of PCK2 gene polymorphism with impaired glucose tolerance after kidney transplantation

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Sources of Funding: none

Introduction

New-onset diabetes mellitus after kidney transplantation (NODAT) is known to be a risk factor for deterioration of graft function and may also cause various fatal complications, including cardiovascular disease after kidney transplantation (KTx). In this study, we focused on genes encoding proteins responsible for the glucose metabolism and determined their single-nucleotide polymorphisms (SNPs). We also examined the correlation between these SNPs and glucose intolerance after KTx.

Methods

This study included 38 patients who underwent KTx at Kobe University Hospital and had normal glucose tolerance prior to KTx. We defined patients with plasma glucose level higher than 140mg/dl at 120 minutes in 75g OGTT at 1 year after KTx as new-onset impaired glucose tolerance (NIGT). We identified 8 SNPs in 7 genes, including, GLUT2 and PCK2, which are involved in glucose metabolism in the liver, as well as IGF2BP2, CDKN2A/B, HHEX and SLC30A8, CDKAL1 which are associated with glucose metabolism in other tissues. We compared the prevalence rate of NIGT among SNPs in each gene.

Results

Out of 38 patients included in this study, 11 patients (28.9%) were diagnosed as NIGT. There was no difference in genotype distribution between transplant and Japanese population samples concerning 8 SNPs in 7 genes. As for rs4982856 in PCK2 gene, the distribution of genotype was, T/T: 11 (28.9 %), T/C: 23 (60.5 %), C/C: 4 (10.5 %) as a whole (table 1). Seven patients out of 11 patients with NIGT had T/T genotype of rs4982856, while only 5 patients out of 27 patients with normal glucose tolerance had T/T genotype of rs4982856. The T allele frequency of the rs4982856 was significantly higher in NIGT than in normal group (81.8 vs. 52.8 %, respectively; p = 0.015; Table 2). Other SNPs were not associated with the risk of glucose intolerance.

Conclusions

Our study indicates that T allele of the rs4982856 in PCK2 gene may be the risk factor for impaired glucose tolerance after kidney transplantation.

Funding

none

Authors
Naoki Yokoyama
Teruyuki Oda
Satoshi Ogawa
Takeshi Ishimura
Masato Fujisawa
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