The Effect of Common Variants in SLC44A2 on the Contribution to the Risk of Deep Cein Thrombosis after Orthopedic Surgery

Aim: Deep vein thrombosis (DVT) is a common complication of orthopedic surgery. Multiple lines of evidence indicate that genetic factors play an important role in the development of DVT following orthopedic surgery (DVTFOS). Recent evidence suggested that the solute carrier family 44 member 2 (SLC44A) gene may contribute to the risk of DVT. In this study, we aimed to investigate the associations of SLC44A2 and DVTFOS in Chinese Han individuals.Methods: In the study, 2,655 subjects, including 689 DVTFOS patients and 1,966 controls, were recruited. Eighteen SNPs were genotyped in the study. Genetic association analyses were performed at both the single marker and haplotype levels. Bioinformatics analyses were conducted to predict the functional consequences of significant SNPs.Results: SNP rs2288904 of SLC44A2 was identified as being significantly associated with DVTFOS (P = 0.0003, OR [95%CI]= 1.28[1.12–1.46]). Allelic analyses showed that the G allele of this SNP significantly elevated the risks of DVTFOS, which was replicated in the genotypic association analyses. Moreover, a two-SNP haplotype, including rs2288904, was found to be strongly correlated with the risk of DVTFOS (P = 4.15 × 10⁻¹¹). Widespread effects in the expression quantitative trait loci were identified for rs2288904 in multiple tissues.Conclusion: In summary, our results provide further supportive evidence of the association of SLC44A2 with the risk of DVTFOS, which also provide clues for understanding the important roles of the SLC44A2 gene in the pathogenesis of DVTFOS and in the development of preventive strategies.