title: Beta-adducin and sodium-calcium exchanger 1 gene variants are associated with systemic lupus erythematosus and lupus nephritis.
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.
authors.affiliation: Unit of Internal Medicine and Immunology, IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy. ramirez.giuseppealvise@hsr.it.|Università Vita-Salute San Raffaele, Milan, Italy. ramirez.giuseppealvise@hsr.it.
authors.forename: Giuseppe A
authors.initials: GA
authors.lastname: Ramirez
authors.affiliation: Unit of Nephrology, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Lanzani
authors.affiliation: Unit of Internal Medicine and Immunology, IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy.
authors.forename: Enrica P
authors.initials: EP
authors.lastname: Bozzolo
authors.affiliation: Unit of Nephrology, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Zagato
authors.affiliation: Unit of Nephrology, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Citterio
authors.affiliation: Unit of Nephrology, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Nunzia
authors.initials: N
authors.lastname: Casamassima
authors.affiliation: Unit of Internal Medicine and Immunology, IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy.|Università Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Canti
authors.affiliation: Unit of Internal Medicine and Immunology, IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy.|Università Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Sabbadini
authors.affiliation: Unit of Internal Medicine and Immunology, IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy.|Università Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Rovere-Querini
authors.affiliation: Università Vita-Salute San Raffaele, Milan, Italy.|Unit of Nephrology, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Manunta
authors.affiliation: Unit of Internal Medicine and Immunology, IRCCS Ospedale San Raffaele, Via Olgettina 60, 20132, Milan, Italy.|Università Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Manfredi
mesh_terms: D000328:Adult; D000483:Alleles; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008181:Lupus Nephritis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019831:Sodium-Calcium Exchanger / Q000235:genetics*; D000099291:Adducins
chemical_list: D002148:Calmodulin-Binding Proteins; D019831:Sodium-Calcium Exchanger; D000099291:Adducins; C110374:sodium-calcium exchanger 1
keywords: Anti-phospholipid antibodies; Arthritis; Beta-adducin; Nephritis; Skin; Sodium–calcium exchanger 1; Systemic lupus erythematosus