Abstract: SA-PO933
Effect of -55C/T Polymorphism of Uncoupling Protein 3 Gene on Risk for New-Onset Diabetes in Chinese Peritoneal Dialysis Patients: A Prospective Cohort Study
Session Information
- Peritoneal Dialysis: Inflammation, Peritoneal Transport
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 703 Dialysis: Peritoneal Dialysis
Authors
- Chen, Yun, Huashan hospital, Fudan university, Shanghai, China
- Dai, Shuqi, Huashan hospital, Fudan university, Shanghai, China
- Shang, Da, Huashan hospital, Fudan university, Shanghai, China
- Hao, Chuan-Ming, Huashan Hosp., Shanghai, SHANGHAI, China
- Zhu, Tongying, Huashan hospital, Fudan university, Shanghai, China
Background
Patients who have no history of glucose intolerance could develop diabetes mellitus after the initiation of PD therapy due to a high glucose load. Different genetic background may result in risk modulation. However, it has been rarely explored among PD patients. Uncoupling protein 3 (UCP3) belongs to a family of mitochondrial transporters and is associated with energy homeostasis. The aim of our study was to investigate the effect of polymorphism of the UCP3 promoter (–55C/T) on the risk of new-onset diabetes mellitus (NODM) in PD patients.
Methods
Non-diabetic patients newly started on PD therapy between May 2005 and March 2018 were recruited (n=150). The -55C/T polymorphism of UCP3 was genotyped in all participants at baseline. Patients were divided into two groups based on the genotypic difference. The cohort was followed for up to 165 months (median: 60.1 months; interquartile range: 34.1 months). Cox regression models were used to analyze the impact of -55C/T polymorphism on risks of NODM. Association between glucose intolerance and genotypes were further ascertained in a second cohort of HOMA-IR low and high subjects.
Results
62 patients (41.3%) had the genotype -55CC (wild group), whereas 88 patients (58.7%) were T carriers (mutant group). During the follow-up, 14 NODM occurred in the mutant group while only 4 occurred in the wild group. Patients in the mutant group experienced significantly higher morbidity (HR: 3.324; 95% CI: 1.088 to 10.151; p = 0.035). Even after adjustments for age, body mass index, total cholesterol, triglycerides, and HOMA-IR, genotypes with T allele remained an independent predictor of NOMD morbidity (HR: 5.804; 95% CI: 1.739 to 19.375; p = 0.004). In the mutant group, HOMA-IR values were higher. Frequencies of the T allele were 27.7% in the HOMA-IR low group compared with 42.1% (p=0.009) in the HOMA-IR high group. The variant of T allele was significantly associated with a higher HOMA-IR value (OR: 2,287; 95% CI:1.177-4.445; p=0.015).
Conclusion
The variant of T allele of UCP3 -55C/T polymorphism was associated with high insulin resistance and was an independent predictor of NODM in PD patients. Early identification of the genotype may provide scientific basis for clinic management of PD patients, improving the surveillance and prevention of diabetes.
Funding
- Other NIH Support