title: TRPC6 gene variants and neuropsychiatric lupus.
abstract: Neuropsychiatric manifestations of systemic lupus erythematosus (NPSLE) influence patients' quality of life and their survival. Little is known about the pathophysiological bases of NPSLE and accordingly there are no specific therapeutic agents to be employed in this setting. Genetic research in systemic lupus erythematosus (SLE) is rapidly evolving as a tool to find clues about the pathogenic determinants of the disease and of its manifestations. Here, we describe the association of a single nucleotide polymorphic variant of the transient receptor potential cation channel, subfamily C, member 6 (TRPC6) gene with protection from the development of NPSLE in a cohort of 106 patients with SLE. TRPC6 is involved in the regulation of N-methyl-d-aspartate (NMDA) receptor signalling, a major player in post-ischemic neuronal injury and in the pathogenesis of NPSLE. TRPC6 genetic variants are promising candidate predictors of nervous system involvement in SLE, whereas the TRPC6 pathway might constitute a potential novel therapeutic target.
authors.affiliation: Unit of Internal Medicine and Immunology, IRCCS Ospedale San Raffaele, Milan, Italy; Università Vita-Salute San Raffaele, Milan, Italy. Electronic address: 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, 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: Lorena
authors.initials: L
authors.lastname: Citterio
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: Nunzia
authors.initials: N
authors.lastname: Casamassima
authors.affiliation: Unit of Internal Medicine and Immunology, IRCCS Ospedale San Raffaele, 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, 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, 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, Milan, Italy; Università Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Manfredi
mesh_terms: D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D020945:Lupus Vasculitis, Central Nervous System / Q000235:genetics* / Q000401:mortality; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016016:Proportional Hazards Models; D050052:TRPC Cation Channels / Q000235:genetics*; D000074287:TRPC6 Cation Channel
chemical_list: D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human
keywords: Genetics; Lupus; Neuropsychiatric involvement; TRPC6