Abstract
BACKGROUND: Venous malformations (VMs) are a common congenital vascular anomaly. The long non-coding RNA (lncRNA) HOTTIP, associated with the HOXA gene cluster, modulates the expression of multiple HOXA genes, which are crucial for vascular development. Abnormal HOXA expression disrupts normal vascular formation. However, no studies have explored the relationship between HOTTIP single nucleotide polymorphisms (SNPs) and the risk of VMs. This study examined whether SNPs in HOTTIP contribute to the development of VMs and their subtypes. METHODS: We conducted a case-control study involving individuals with VMs, collecting blood samples from 1,113 patients with VM and 1,158 healthy controls. TaqMan genotyping of the lncRNA HOTTIP rs3807598 C>G was performed using real-time fluorescence quantitative polymerase chain reaction (PCR) on the Applied Biosystems 7,900HT Fast Real-Time PCR System. RESULTS: Our multivariate logistic regression analysis found no significant correlation between the rs3807598 C>G polymorphism in HOTTIP and VM susceptibility in the general population (P>0.05). Stratification by site of origin revealed that the rs3807598 GG genotype was associated with an increased risk of upper-extremity VMs [adjusted odds ratio (OR) =1.55; 95% confidence interval (CI): 1.002-2.39; P=0.049]. CONCLUSIONS: Our study showed that HOTTIP rs3807598 C>G was not associated with VM risk. Further studies are needed to elucidate the interaction between the HOTTIP rs3807598 polymorphism and genetic and environmental factors to reveal its role in the pathogenesis of VM.