Plasminogen activator inhibitor-1 5G/5G genotype is a protecting factor preventing posttransplant diabetes mellitus.
OBJECTIVE
Plasminogen activator inhibitor 1 (PAI-1) is thought to play a role in the pathogenesis of obesity and insulin resistance. A connection between gestational diabetes mellitus and the functional -675 PAI-1 genotype has been reported. Therefore, we examined the role of the PAI-1 gene polymorphism in kidney transplant recipients.


METHODS
A total of 376 kidney transplant recipients were prospectively screened for posttransplant diabetes mellitus (PTDM). Eighty-one (21.5%) patients were diagnosed with PTDM and the other 295 patients were non-diabetic following kidney transplantation. DNA samples were isolated from the sera and analyzed for the functional -675 4G/5G promoter polymorphisms of the PAI-1 gene.


RESULTS
Kidney transplant recipients with PTDM were significantly associated with tacrolimus use (p=0.03), older age (p=0.036), and higher body mass index (p=0.001). The genotype distribution was significantly different between the patients with PTDM (genotype 4G/4G:4G/5G:5G/5G=33.3%:60.5%:6.2%) and those without PTDM (genotype 4G/4G:4G/5G:5G/5G=36.9%:44.1%:19.0%) (p=0.018). Patients with homozygosity for 5G had a significantly lower rate of PTDM (aOR, 0.286, p=0.022) and higher cumulative event-free probability of time to PTDM (log rank test, p=0.0058).


CONCLUSIONS
Homozygosity for the 5G allele of the PAI-1 gene constitutes a protecting factor for the development of PTDM. Our findings are similar to a previous study on gestational diabetes mellitus, and strongly support a possible genetic role of PAI-1 in the development of PTDM.
Division of Nephrology, Department of Medicine, Chung Shan Medical University Hospital, Taichung 402, Taiwan. chr@csmu.edu.tw
Horng-Rong
HR
Chang
Shun-Fa
SF
Yang
Jen-Pi
JP
Tsai
Ming-Chia
MC
Hsieh
Sheng-Wen
SW
Wu
Hui-Ching
HC
Tsai
Tung-Wei
TW
Hung
Jun-Huang
JH
Huang
Jong-Da
JD
Lian
D000328:Adult; D003920:Diabetes Mellitus / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D011183:Postoperative Complications / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control*; D011446:Prospective Studies; D012044:Regression Analysis
D017395:Plasminogen Activator Inhibitor 1