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. 2023 Oct;60(10):1351-1358.
doi: 10.1007/s00592-023-02128-6. Epub 2023 Jun 20.

IGF1 and PPARG polymorphisms are associated with reduced estimated glomerular filtration rate in a cohort of children and adolescents with type 1 diabetes

Chiara Zusi #  1 , Marco Rioda #  2 , Alice Maguolo  2 , Federica Emiliani  2 , Ilaria Unali  2 , Silvia Costantini  2 , Massimiliano Corradi  2 , Giovanna Contreas  2 , Anita Morandi  2 , Claudio Maffeis  2
Affiliations

IGF1 and PPARG polymorphisms are associated with reduced estimated glomerular filtration rate in a cohort of children and adolescents with type 1 diabetes

Chiara Zusi et al. Acta Diabetol. 2023 Oct.

Abstract

Introduction: Several genetic loci have been associated with diabetic nephropathy; however, the underlying genetic mechanisms are still poorly understood, with no robust candidate genes identified yet.

Aim: We aimed to determine whether two polymorphisms, previously associated with renal decline, influence kidney impairment evaluating their association with markers of renal function in a pediatric population with type 1 diabetes (T1D).

Material and methods: Renal function was evaluated by glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) in a cohort of pediatric subjects with T1D (n = 278). Risk factors for diabetes complications (diabetes duration, blood pressure, HbA1c) were assessed. The IGF1 rs35767 and PPARG rs1801282 SNPs were genotyped by TaqMan RT-PCR system. An additive genetic interaction was calculated. Association analysis between markers of renal function and both SNPs or their additive interaction were performed.

Results: Both SNPs showed a significant association with eGFR: the A allele of rs35767 or the C allele of rs1801282 were associated to reduced eGFR compared to G alleles. Multivariate regression analysis adjusted for age, sex, z-BMI, T1D duration, blood pressure and Hba1c values showed that the additive genetic interaction was independently associated with lower eGFR (β = -3.59 [-6.52 to -0.66], p = 0.017). No associations were detected between SNPs, their additive interaction and ACR.

Conclusions: These results provide new insight into the genetic predisposition to renal dysfunction, showing that two polymorphisms in IGF1 and PPARG genes can lead to a reduction in renal filtration rate leading these patients to be exposed to a higher risk of early renal complications.

Keywords: Diabetic nephropathy; IGF1; PPARG; T1D.

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Conflict of interest statement

The authors declare that they have no conflicts of interests in this work.

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