Abstract
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.
Funder
Università degli Studi di Verona
Publisher
Springer Science and Business Media LLC
Subject
Endocrinology,General Medicine,Endocrinology, Diabetes and Metabolism,Internal Medicine
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