Association between VDR gene FokI polymorphism and renal function in patients with IgA nephropathy

Mo, Manqiu; Pan, Ling; Tan, Lin; Jiang, Ling; Pan, Yongqing; Li, Fuji; Yang, Zhenhua; Liao, Yunhua

doi:10.7717/peerj.7092

Cited by 6 publications

(5 citation statements)

References 41 publications

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“…Many previous studies on dyslipidemia have revealed that it is not only a risk factor for the occurrence and development of cardiovascular diseases but aggravates the progression and prognosis of IgAN [10]. Research has shown that the incidence of dyslipidemia in adult IgAN is 45.3-61.1% [9,18,19]. At present, there are few studies on the clinicopathological characteristics and renal outcomes of IgAN complicated with dyslipidemia in China.…”

Section: Discussionmentioning

confidence: 99%

“…Dyslipidemia is present in many chronic kidney disease (CKD) patients, and it is also one of the independent risk factors for the progression of kidney disease [8]. Several lines of evidence have suggested that dyslipidemia is related to clinical symptoms, disease progression, and prognosis of the patients with IgAN [9,10], and it is also a risk factor for IgAN to enter ESRD [11]. Nevertheless, few studies involve pathological factors (especially the Oxford classification).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Clinicopathological Characteristics and Outcomes of Immunoglobulin A Nephropathy with Different Types of Dyslipidemia: A Retrospective Single-Center Study

Han

et al. 2023

Kidney Blood Press Res

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Introduction: Immunoglobulin A nephropathy (IgAN) is one of the most common glomerulonephritic diseases in the world. Several lines of evidence have suggested that dyslipidemia is related to the disease progression and prognosis of IgAN. However, the study is scarce on the clinicopathological characteristics and outcomes of IgAN with dyslipidemia. Methods: This study retrospectively analyzed 234 patients with biopsy-proven idiopathic IgAN at the Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, between January 2015 and June 2021. The participants were divided into dyslipidemia (n = 119) and non-dyslipidemia (n = 115), and the dyslipidemia group was also divided into the following 4 groups: hypertriglyceridemia group, hypercholesterolemia group, mixed hyperlipidemia group, and low high-density lipoprotein cholesterol group. The estimated glomerular filtration rate (eGFR) was estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Results: The prevalence of dyslipidemia in IgAN patients in our center was 50.9% (119/234). The patients with dyslipidemia presented with higher systolic blood pressure (BP), diastolic BP, serum creatinine, uric acid, hemoglobin, proteinuria, and eGFR (p < 0.05). Proportions of males, hypertension, and chronic kidney disease stage 2∼5 were also higher in the dyslipidemia group (p < 0.05). Similarly, the pathological characteristics performed were worse in the dyslipidemia group. Most dyslipidemia patients had a higher percentage of mesangial hypercellularity (M1) and tubular atrophy/interstitial fibrosis (T1∼2) in the Oxford Classification’s scoring system (p < 0.05). Multivariate logistic regression analysis revealed that male gender (odds ratio [OR] = 2.397, 95% confidence interval [CI]: 1.051–5.469, p = 0.038) and proteinuria (OR = 1.000, 95% CI: 1.000–1.001, p = 0.035) were possible risk factors for dyslipidemia. A total of 13 patients (13.8%) in the dyslipidemia group had an endpoint event, of which 6 patients (6.4%) had a ≥50% decrease in eGFR from baseline and 7 patients (7.4%) reached the end-stage renal disease stage. Kaplan-Meier survival curve analysis showed that patients in the dyslipidemia group had a worse outcome than those in the non-dyslipidemia group (log-rank test, p = 0.048). Conclusions: IgAN patients with dyslipidemia presented more severe clinicopathological characteristics. Male gender and proteinuria are significantly associated with the occurrence of dyslipidemia in IgAN patients. Patients in the dyslipidemia group had a worse prognosis than those in the non-dyslipidemia group, which may be essential for the disease management of IgAN and help identify the high-risk patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinicopathological Characteristics and Outcomes of Immunoglobulin A Nephropathy with Different Types of Dyslipidemia: A Retrospective Single-Center Study

Han

et al. 2023

Kidney Blood Press Res

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“…Mo et al reported higher levels of blood urea nitrogen, serum phosphorus, mesangial cellularity/cell proliferation, interstitial fibrosis/tubular atrophy and crescents in VDR rs2228570T allele carriers compared with non-T allele carriers, whereas eGFR and 25-Hydroxyvitamin D3 were lower in T-allele carriers compared with non-T allele carriers among IgAN patients, indicating a role for VDR in the pathogenesis of IgAN [33]. ADM, a vasodilator peptide abundantly expressed in kidneys, shows enrichment with pathways that positively regulate apoptosis.…”

Section: Plos Onementioning

confidence: 99%

Genome-wide analysis of long noncoding RNAs as cis-acting regulators of transcription factor-encoding genes in IgA nephropathy

Zhai,

Tian,

Zhang

et al. 2024

PLoS ONE

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Background IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis in the world, but the disease pathogenesis noncoding is yet to be elucidated. Previous studies have revealed regulatory functions for long noncoding RNA (lncRNA) in various diseases; however, the roles of lncRNA in IgAN and regulation of transcription factors (TFs) have been scarcely investigated. Methods Renal tissue samples (n = 5) from patients with IgAN and control samples (n = 4) were collected and RNA sequencing (RNA-seq) was performed. Four software programs were employed for lncRNA prediction. GO (Gene Ontology)/KEGG (Kyoto Encyclopedia of Genes and Genomes) were employed for analysis of the identified differentially expressed genes (DEGs). A regulatory network model of DE lncRNA-TF-DEG was developed, and the levels of expression of key lncRNAs, TFs, and corresponding target genes were assessed using qRT-PCR and immunofluorescence. Results The current study identified 674 upregulated and 1,011 downregulated DE mRNAs and 260 upregulated and 232 downregulated DE lncRNAs in IgAN samples compared with control samples. The upregulated DE mRNAs showed enrichment in cell adhesion and collagen glial fiber organization pathways. The DE lncRNAs-DE mRNAs showing co-expression are associated with transmembrane transport. A novel regulatory network model of lncRNA-TF-DEG has been developed. This study identified seven TFs that are cis-regulated by 6 DE lncRNAs, and show co-expression with 132 DEGs (correlation coefficient ≥ 0.8, P ≤ 0.01), generating 158 pairs that showed co-expression. The lncRNAs NQO1-DT and RP5-1057120.6 were found to be highly expressed in IgAN samples. The TFs vitamin D Receptor (VDR) and NFAT5, along with their target genes were also aberrantly expressed. Conclusion Key lncRNAs and TFs centrally associated with IgAN have been identified in this study. A regulatory network model of lncRNA-TF-mRNA was constructed. Further studies on the genes identified herewith could provide insight into the pathogenesis of IgAN.

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“…Genetic causes guide the occurrence and progression of IgAN: Shi et al [ 126 ] demonstrated that IgAN progression in subjects with moderate and high genetic risk was 2.12- and 3.61-fold higher than in those with low genetic risk. In support of this concept, Mo et al [ 127 ] studied the relationship between VDR FokI single nucleotide polymorphism and renal function in IgA patients: the subjects presenting VDR FokI TT genotype had an increased risk of renal dysfunction, demonstrating a potential utility in prediction of the progression of the disease. VDR polymorphisms may aggravate IgAN by inhibiting active vitamin D’s protective role, worsening endothelial cells dysfunction, mesangial cell proliferation, and podocyte and tubulointerstitial damage [ 128 ].…”

Section: Vitamin D In Iga Nephropathymentioning

confidence: 99%

Vitamin D and Glomerulonephritis

et al. 2021

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Vitamin D presents a plethora of different functions that go beyond its role in skeletal homeostasis. It is an efficient endocrine regulator of the Renin–Angiotensin–Aldosterone System (RAAS) and erythropoiesis, exerts immunomodulatory effects, reduces the cardiovascular events and all-cause mortality. In Chronic Kidney Disease (CKD) patients, Vitamin D function is impaired; the renal hydrolyzation of its inactive form by the action of 1α-hydroxylase declines at the same pace of reduced nephron mass. Moreover, Vitamin D major carrier, the D-binding protein (DBP), is less represented due to Nephrotic Syndrome (NS), proteinuria, and the alteration of the cubilin–megalin–amnionless receptor complex in the renal proximal tubule. In Glomerulonephritis (GN), Vitamin D supplementation demonstrated to significantly reduce proteinuria and to slow kidney disease progression. It also has potent antiproliferative and immunomodulating functions, contributing to the inhibitions of kidney inflammation. Vitamin D preserves the structural integrity of the slit diaphragm guaranteeing protective effects on podocytes. Activated Vitamin D has been demonstrated to potentiate the antiproteinuric effect of RAAS inhibitors in IgA nephropathy and Lupus Nephritis, enforcing its role in the treatment of glomerulonephritis: calcitriol treatment, through Vitamin D receptor (VDR) action, can regulate the heparanase promoter activity and modulate the urokinase receptor (uPAR), guaranteeing podocyte preservation. It also controls the podocyte distribution by modulating mRNA synthesis and protein expression of nephrin and podocin. Maxalcalcitol is another promising alternative: it has about 1/600 affinity to vitamin D binding protein (DBP), compared to Calcitriol, overcoming the risk of hypercalcemia, hyperphosphatemia and calcifications, and it circulates principally in unbound form with easier availability for target tissues. Doxercalciferol, as well as paricalcitol, showed a lower incidence of hypercalcemia and hypercalciuria than Calcitriol. Paricalcitol demonstrated a significant role in suppressing RAAS genes expression: it significantly decreases angiotensinogen, renin, renin receptors, and vascular endothelial growth factor (VEGF) mRNA levels, thus reducing proteinuria and renal damage. The purpose of this article is to establish the Vitamin D role on immunomodulation, inflammatory and autoimmune processes in GN.

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Association between VDR gene FokI polymorphism and renal function in patients with IgA nephropathy

Cited by 6 publications

References 41 publications

Clinicopathological Characteristics and Outcomes of Immunoglobulin A Nephropathy with Different Types of Dyslipidemia: A Retrospective Single-Center Study

Clinicopathological Characteristics and Outcomes of Immunoglobulin A Nephropathy with Different Types of Dyslipidemia: A Retrospective Single-Center Study

Genome-wide analysis of long noncoding RNAs as cis-acting regulators of transcription factor-encoding genes in IgA nephropathy

Vitamin D and Glomerulonephritis

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