Association between functional variant of inflammatory system gene (PSMA6) and end-stage kidney disease

Abstract

BackgroundThe proteasome system is involved in several disorders. The 5′ untranslated region of PSMA6 gene contains a single nucleotide polymorphism (SNP) −8 C/G, associated with diabetes, myocardial infarction and coronary artery disease.MethodsWe examined 584 patients with end-stage kidney disease (ESKD) and 430 controls. All were genotyped for −8 C/G SNP by polymerase chain reaction and restriction analysis.ResultsWe observed lower frequency of CG + GG genotypes in patients than in controls (20 vs. 42 %, p = 0.0038). The odds ratio of 0.34 (95 % CI 0.26–0.45) suggests association of CG + GG with decreased risk of ESKD. We investigated the association between PSMA6 polymorphism and LVH present in 54 % of patients. There was a significant association of CG + GG genotype with LVH, with over 75 % of CG + GG in patients with LVH. This effect was independent from other common causes of LVH—age (OR 1.12, p = 0.643) and hypertension (OR 1.72, p = 0.422).ConclusionWe demonstrated for the first time that PSMA6 polymorphism might be a protective factor for ESKD. On the other hand, CG + GG genotypes are independently related to LVH in ESKD patients.

The Genetic Variants of NOTCH3 (6746T>C) and PSMA6 (-8C>G) as Possible Risk Factors of Psoriasis Development

“…In turn, an altered expression of PSMA6 gene may increase inflammation through activation of the NF-kB protein [ 23 ]. Similar to our results, the PSMA6 CC genotype was previously demonstrated to be more common in the patients with the endstage of renal disease than in controls (80% vs. 58%, respectively), which suggested a protective role of the G allele [ 28 ]. In our study, the PSMA6 G allele carrier frequency was similar in the psoriatic patients and healthy controls.…”

The Genetic Variants of NOTCH3 (6746T>C) and PSMA6 (-8C>G) As Possible Risk Factors of Psoriasis Development

“…Similarly to our results, the PSMA6 CC genotype was previously demonstrated to be more common in the patients with the end-stage of renal disease than in controls (80% vs. 58%, respectively), which suggested a protective role of the G allele 25 . In our study, the PSMA6 G allele carrier frequency was similar in the psoriatic patients and controls.…”

Proteasome subunit-α type-6 protein is post-transcriptionally repressed by the microRNA-4490 in diabetic nephropathy

“…The down-regulated miRNAs, inclusive of miR-29, miR-141, and miR-200, seem to be rendering renal protective effect by reducing expression of TGF-β2, COL1, COL4, and NADPH oxidase subunit 4 all factors involved in the pathophysiology of diabetic nephropathy [ 13 , 14 , 17–19 ]. The PSMA6 gene has been shown to harbor single nucleotide polymorphism, including a 5’-UTR 8 C/G, associated with diabetes, and that PSMA6 polymorphism might be a protective factor for ESRD [ 20 , 21 ]. Our results show that exogenous manipulation of miR-4490 levels can modulate expression of PSMA6, indicating that miR-4490 can be tested as a potential biomarker for nephropathy in diabetic patients.…”