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Beta-adducin and sodium–calcium exchanger 1 gene variants are associated with systemic lupus erythematosus and lupus nephritis

  • Original Article - Genes and Disease
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Abstract

Genetic research in systemic lupus erythematosus (SLE) is rapidly developing, and numerous sets of genes are being associated with specific clinical subphenotypes in the setting of SLE. On the other hand, basic science studies are revealing strong connections between salt–water balance and inflammation. The aim of this study was to evaluate whether variants of genes known to influence the individual susceptibility to hypertension also influence the renal function in a cohort of SLE patients with and without lupus nephritis (LN). This study is a case–control study with candidate gene approach. A total of 111 patients with SLE (50 with SLE without nephritis, 55 with LN and 6 with simple urinary sediment abnormalities) and 62 healthy controls (HC) were genotyped for NCX1 rs11893826 (NCX1a) and rs434082 (NCX1b) and ADD2 rs4984 SNPs. Patients with ADD2 CT genotype were protected from LN and skin involvement; ADD2 CC | NCX1a AA/AG genotypes were associated with the presence of anti-cardiolipin antibodies; NCX1a AA genotype was slightly more frequent in lupus patients than in HC and associated with relapse risk and higher creatinine in patients with LN. NCX1b GG patients with LN had increased chances to reach complete remission. NCX1b GG | NCX1a GG genotype is associated with joint involvement. ADD2 and NCX1 variants influence the risk and the clinical features of SLE and LN, highlighting their potential role in regulating systemic inflammation and/or the local response to immune-mediated injury.

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Abbreviations

ADD2:

Beta-adducin gene

CR:

Complete remission

HC:

Healthy controls

LLAC:

Lupus-like anticoagulants

LN:

Lupus nephritis

NCX1:

Solute carrier family 8 (sodium–calcium exchanger) member 1 gene

OR:

Odds ratio

SLE:

Systemic lupus erythematosus

SLEnonLN:

SLE without LN

SNP:

Single-nucleotide polymorphism

SUA:

Simple urinary sediment abnormalities

WLC:

Whole lupus cohort

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Acknowledgments

The authors wish to thank all members of the staff of the Unit of Internal Medicine and Immunology at San Raffaele Hospital for their assistance in data and blood sample collection. We would also like to thank the Italian Association of Patients with SLE (Gruppo LES Italiano) for supporting the presentation of part of this work in a previous congress. The work was supported by the Italian Ministry of Health (Fondo per gli Investimenti della Ricerca di Base-IDEAS to P.R.-Q. and Ricerca Finalizzata to A.A.M. and P.R.-Q.), the Italian Association for Cancer Research (AIRC; to A.A.M.) and the Italian Ministry for School Univeristy and Research (to A.A.M.).

Conflict of interest

The authors declare that there is no conflict of interest.

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Authors and Affiliations

  1. Unit of Internal Medicine and Immunology, IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy

    Giuseppe A. Ramirez, Enrica P. Bozzolo, Valentina Canti, Maria Grazia Sabbadini, Patrizia Rovere-Querini & Angelo A. Manfredi

  2. Università Vita-Salute San Raffaele, Milan, Italy

    Giuseppe A. Ramirez, Valentina Canti, Maria Grazia Sabbadini, Patrizia Rovere-Querini, Paolo Manunta & Angelo A. Manfredi

  3. Unit of Nephrology, IRCCS Ospedale San Raffaele, Milan, Italy

    Chiara Lanzani, Laura Zagato, Lorena Citterio, Nunzia Casamassima & Paolo Manunta

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  1. Giuseppe A. Ramirez
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Correspondence to Giuseppe A. Ramirez.

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Ramirez, G.A., Lanzani, C., Bozzolo, E.P. et al. Beta-adducin and sodium–calcium exchanger 1 gene variants are associated with systemic lupus erythematosus and lupus nephritis. Rheumatol Int 35, 1975–1983 (2015). https://doi.org/10.1007/s00296-015-3298-x

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  • DOI: https://doi.org/10.1007/s00296-015-3298-x

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