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接受他克莫司治疗的肾移植术后糖尿病患者的瘦素受体基因多态性

Leptin receptor gene polymorphisms in kidney transplant patients with post-transplant diabetes mellitus treated with tacrolimus.

作者信息

Dziedziejko Violetta, Safranow Krzysztof, Kijko-Nowak Mirosława, Malinowski Damian, Domanski Leszek, Pawlik Andrzej

机构信息

Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, 70-111 Szczecin, Poland.

Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, 70-111 Szczecin, Poland.

出版信息

Int Immunopharmacol. 2023 Nov;124(Pt B):110989. doi: 10.1016/j.intimp.2023.110989. Epub 2023 Sep 28.

Abstract

Post-transplant diabetes mellitus (PTDM) is a metabolic complication that often occurs after kidney transplantation. Factors that increase the risk of this complication are currently being researched, including polymorphisms in genes affecting carbohydrate-lipid metabolism. Leptin is a hormone that affects appetite and adipose tissue and plays an important role in regulating insulin secretion as well as glucose and lipid metabolism. The aim of this study was to examine the association between leptin receptor gene polymorphisms and the development of post-transplant diabetes mellitus in patients treated with tacrolimus. The study was carried out in a group of 201 patients who underwent kidney transplantation. The follow-up period was 12 months. PTDM was diagnosed in 35 patients. Analysing the LEPR gene rs1137101 polymorphism, we observed in patients with PTDM an increased frequency of GG genotype carriers (GG vs AA, OR 3.36; 95 % CI 0.99-11.46; p = 0.04). There were no statistically significant differences in the distribution of the LEPR rs1137100 and LEPR rs1805094 polymorphisms between patients with and without PTDM. Multivariate regression analysis confirmed that female sex, advanced age, increased BMI and a higher number of LEPR rs1137101 G alleles were independent risk factors for PTDM development. The risk of PTDM development was almost 3.5 times greater in LEPR rs1137101 G allele carriers than in AA homozygotes (GG + AG vs AA; OR 3.48; 95 %CI (1.09-11.18), p = 0.035). The results suggest that patients after kidney transplantation with the LEPR gene rs1137101 G allele may have an increased risk of post-transplant diabetes development.

摘要

移植后糖尿病(PTDM)是一种常在肾移植后出现的代谢并发症。目前正在研究增加这种并发症风险的因素,包括影响碳水化合物 - 脂质代谢的基因多态性。瘦素是一种影响食欲和脂肪组织的激素,在调节胰岛素分泌以及葡萄糖和脂质代谢中起重要作用。本研究的目的是探讨接受他克莫司治疗的患者中瘦素受体基因多态性与移植后糖尿病发生之间的关联。该研究在一组201例接受肾移植的患者中进行。随访期为12个月。35例患者被诊断为PTDM。分析LEPR基因rs1137101多态性时,我们观察到PTDM患者中GG基因型携带者的频率增加(GG与AA相比,OR 3.36;95%CI 0.99 - 11.46;p = 0.04)。有无PTDM的患者之间,LEPR rs1137100和LEPR rs1805094多态性的分布没有统计学上的显著差异。多变量回归分析证实,女性、高龄、BMI增加以及LEPR rs1137101 G等位基因数量增加是PTDM发生的独立危险因素。LEPR rs1137101 G等位基因携带者发生PTDM的风险几乎是AA纯合子的3.5倍(GG + AG与AA相比;OR 3.48;95%CI(1.09 - 11.18),p = 0.035)。结果表明,肾移植后携带LEPR基因rs1137101 G等位基因的患者发生移植后糖尿病的风险可能增加。

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