Publication:
FLT3 functional low-frequency variant rs76428106-C is associated with susceptibility to systemic sclerosis.

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Date

2022-07-11

Authors

Martinez-Lopez, Javier
Kerick, Martin
Ortiz-Fernandez, Lourdes
Acosta-Herrera, Marialbert
Marquez, Ana
Martin, Javier

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Oxford University Press
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Abstract

rs76428106-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.

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MeSH Terms

Humans
Genetic Predisposition to Disease
Genome-Wide Association Study
Polymorphism, Single Nucleotide
Scleroderma, Systemic
Genotype
Autoimmune Diseases
Case-Control Studies
fms-Like Tyrosine Kinase 3

DeCS Terms

Enfermedades autoinmunes
Esclerodermia sistémica
Estudio de asociación del genoma completo
Estudios de casos y controles Genotipo
Humanos
Polimorfismo de nucleótido simple
Predisposición genética a la enfermedad
Tirosina Quinasa 3 similar a fms

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Keywords

SSc, low-frequency variant, seropositive immune-mediated diseases

Citation

Martínez-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-SI142