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The rs3931283/PVT1 and rs7158663/MEG3 polymorphisms are associated with diabetic kidney disease and markers of renal function in patients with type 2 diabetes mellitus

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Abstract

Background

Long non-coding RNAs (lncRNAs) are key regulators of gene expression. Some studies have reported the association of polymorphisms in lncRNA genes with diabetes mellitus (DM) and its chronic complications, including diabetic kidney disease (DKD); however, the results are still inconclusive. Thus, we investigated the association of the rs3200401/MALAT1, rs1894720/MIAT, rs3931283/PVT1, rs11993333/PVT1, rs5749201/TUG1, and rs7158663/MEG3 polymorphisms with DKD in patients with type 2 DM (T2DM).

Methods and results

This study comprised 902 patients with T2DM and DKD (cases) and 394 patients with T2DM without DKD (controls). The six polymorphisms of interest were genotyped by real-time PCR using TaqMan probes. Frequency of the rs3931283/PVT1 G/G genotype was 36.2% in cases and 31.9% in controls (P = 0.331). After adjustment for gender, glycated hemoglobin, HDL cholesterol, ethnicity, hypertension, and diabetic retinopathy, the G/G genotype was associated with risk for DKD (OR = 1.625, 95% CI 1.020–2.588; P = 0.041). The rs3931283/PVT1 G/G genotype was also associated with higher urinary albumin excretion levels compared to A allele carriers (P = 0.017). No difference was found in rs7158663/MEG3 genotype frequencies between T2DM controls and DKD patients (OR = 1.087, 95% CI 0.686–1.724; P = 0.722). However, the rs7158663/MEG3 G/G genotype was associated with protection against severe DKD (OR = 0.694, 95% CI 0.488–0.989; P = 0.043, for patients with severe DKD vs. T2DM controls). The rs7158663/MEG3 G/G genotype was also associated with lower creatinine levels (P = 0.007) and higher estimated glomerular filtration rate (P = 0.010) compared to A allele carriers. No association was found between the rs11993333/PVT1, rs3200401/MALAT1, rs1894720/MIAT, and rs5749201/TUG1 polymorphisms and DKD or its laboratory markers.

Conclusion

The rs3931283/PVT1 G/G and rs7158663/MEG3 G/G are associated with DKD and markers of renal function in T2DM patients from a Brazilian population.

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Acknowledgements

This study was partially supported by grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundo de Incentivo à Pesquisa e Eventos (FIPE) at Hospital de Clínicas de Porto Alegre (grant number: 2020 − 0656), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS) (Edital FAPERGS/CNPq PRONEX 12/2014: 16-2551-0000476-5) ( FAPERGS 05/2019 – Programa Pesquisador Gaúcho PqG), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Graduate Program in Medical Sciences: Endocrinology – Universidade Federal do Rio Grande do Sul. D.C., and L.H.C are recipients of scholarship from CNPq; C.D. and F.M.P are recipient of scholarships from CAPES; and E.G. is a recipient of a scholarship from FAPERGS.

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Authors and Affiliations

  1. Endocrine Division, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350; prédio 12; 4° andar, 90035-003, Porto Alegre, Rio Grande do Sul, Brazil

    Cristine Dieter, Natália Emerim Lemos, Eliandra Girardi, Denise Taurino Ramos, Felipe Mateus Pellenz, Luís Henrique Canani, Taís Silveira Assmann & Daisy Crispim

  2. Graduate Program in Medical Sciences: Endocrinology, Faculty of Medicine, Department of Internal Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil

    Cristine Dieter, Felipe Mateus Pellenz, Luís Henrique Canani, Taís Silveira Assmann & Daisy Crispim

  3. Department of Biochemistry, Institute of Chemistry, Universidade de São Paulo, São Paulo, Brazil

    Natália Emerim Lemos

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Contributions

Cristine Dieter and Daisy Crispim contributed to the study conception and design. Material preparation and data collection were performed by Cristine Dieter, Natália Emerim Lemos, Felipe Mateus Pellenz, Eliandra Girardi and Denise Taurino Ramos. Statistical Analysis was performed by Cristine Dieter, Natália Emerim Lemos, Taís Silveira Assmann and Daisy Crispim. Data Interpretation was performed by Cristine Dieter, Natália Emerim Lemos, Luís Henrique Canani, Taís Silveira Assmann, Daisy Crispim. The first draft of the manuscript was written by Cristine Dieter and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Daisy Crispim.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee in Research from Hospital de Clínicas de Porto Alegre (number 2020 − 0656). All subjects provided assent and written informed consent prior the inclusion in the study.

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Dieter, C., Lemos, N.E., Girardi, E. et al. The rs3931283/PVT1 and rs7158663/MEG3 polymorphisms are associated with diabetic kidney disease and markers of renal function in patients with type 2 diabetes mellitus. Mol Biol Rep 50, 2159–2169 (2023). https://doi.org/10.1007/s11033-022-08122-5

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