Genetic and genomic associations in antiphospholipid syndrome: A systematic review

Numerous genes have been associated with APS in the literature. In recent years, microRNA (miRNA) and long non-coding RNA (lncRNA) have also been shown to modulate the expression of APS-related genes.

We performed a systematic review to identify all studies reporting on genetic mechanisms that have been shown to be associated with APS.

An extensive literature search was performed in the PubMed, Cochrane and Web of Science databases gathering all available articles through February 2024. We only selected case-control studies that met inclusion criteria and that focused on genetic contributors and modifiers related to primary APS.

Sixty studies were selected for data extraction. Selected studies were grouped into 8 broad categories for review and analysis: (1) gene expression studies; (2) thrombophilia genotypes; (3) single nucleotide polymorphisms (SNPs); (4) interferon-inducible genes; (5) microRNA studies; (6) long non-coding RNA (lncRNA) studies; (7) DNA methylation studies; and (8) differential gene expression studies. Several genes have been identified as associated with APS by more than one approach, including TF, complement associated genes, and interferon-inducible genes. It has been demonstrated that miRNA and lncRNA may alter the expression of important genes in patients with APS.

This systematic review has helped highlight important genes implicated in APS. Most importantly, pathways such as thrombosis/hemostasis, complement and interferon appear to be involved. Further studies are needed to help uncover important genes that could serve as biomarkers.