Martinez-Lopez, JavierKerick, MartinOrtiz-Fernandez, LourdesAcosta-Herrera, MarialbertMarquez, AnaMartin, Javier2023-05-032023-05-032022-07-11Martínez-López J, Kerick M, Ortiz-Fernández L, Acosta-Herrera M, Márquez A, Martín J. FLT3 functional low-frequency variant rs76428106-C is associated with susceptibility to systemic sclerosis. Rheumatology (Oxford). 2023 Feb 6;62(SI):SI138-SI142http://hdl.handle.net/10668/19834rs76428106-C, a low frequency polymorphism that affects the splicing of the FLT3 gene, has recently been associated with several seropositive autoimmune diseases. Here, we aimed to evaluate the potential implication of rs76428106-C in the susceptibility to systemic sclerosis (SSc). We analysed a total of 26 598 European ancestry individuals, 9063 SSc and 17 535 healthy controls, to test the association between FLT3 rs76428106-C and SSc and its different subphenotypes. Genotype data of rs76428106 were obtained by imputation of already available genome-wide association study data and analysed by logistic regression analysis. In accordance with that observed in other autoimmune disorders, the FLT3 rs76428106-C allele was significantly increased [P-value = 2.03 × 10-3, odds ratio (OR) = 1.34] in SSc patients compared with healthy controls. A similar risk effect was found when the main SSc clinical and serological subgroups were compared with controls. When comparing SSc patients with and without digital ulcers (DU), the rs76428106-C frequency was significantly increased in DU-positive SSc patients in comparison with DU-negative patients (P-value = 0.036, OR = 2.16). This study is the first to report an association between rs76428176-C and SSc. Our results support the role of FLT3 as a relevant gene in seropositive immune-mediated diseases and a potential biomarker for SSc microangiopathy.enAttribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/SSclow-frequency variantseropositive immune-mediated diseasesHumansGenetic Predisposition to DiseaseGenome-Wide Association StudyPolymorphism, Single NucleotideScleroderma, SystemicGenotypeAutoimmune DiseasesCase-Control Studiesfms-Like Tyrosine Kinase 3research article35876828open accessEnfermedades autoinmunesEsclerodermia sistémicaEstudio de asociación del genoma completoEstudios de casos y controles GenotipoHumanosPolimorfismo de nucleótido simplePredisposición genética a la enfermedadTirosina Quinasa 3 similar a fms10.1093/rheumatology/keac4061462-0332PMC9910569https://academic.oup.com/rheumatology/advance-article-pdf/doi/10.1093/rheumatology/keac406/45095811/keac406.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9910569/pdf