Abstract
Objective The aim of this study is to evaluate the association of genetic polymorphisms in Cytochrome P450 2D6(CYP2D6) and the change in VEGF levels with the response to propranolol in patients with Infantile hemangiomas (IH). Methods IH patients who underwent over six months of propranolol therapy and received oral propranolol only were enrolled. The target dose of propranolol was 1 mg kg−1day−1. Deoxyribonucleic acid was obtained from venous blood leukocytes. Genotypes of CYP2D6 (rs1065852 and rs1135840) were tested by polymerase chain reaction (PCR) and by sequencing the products. Baseline serum VEGF and serum VEGF one month after treatment were measured. The clinical responses after six months of treatment were evaluated. Genotypes of CYP2D6 (rs1065852 and rs1135840) and VEGF levels were compared between good responders and poor-to-moderate responders. Results 72 patients were enrolled in the study. Patients with CYP2D6 (rs1135840) G/G homozygote had the highest response rate to propranolol. No significant association was found between the response rates and CYP2D6 (rs1065852) polymorphism. No significant differences were found in baseline serum VEGF, serum VEGF one month after treatment, and VEGF ratio between good responders and poor-to-moderate responders. Conclusion The response to propranolol treatment in IH patients was associated with the gene polymorphism of CYP2D6 (rs1135840). A low-dose propranolol regimen was effective and safe in young infants with IH. The change of serum VEGF levels after one month's treatment could not be used to predict the response rate to propranolol.
Highlights
Infantile hemangiomas (IH) occur in 3% to 10% of infants [1]
Between June 2017 and January 2019, children with newly diagnosed IH who underwent over six months of propranolol therapy and received oral propranolol only were enrolled in the study
IH can be morphologically categorized into 4 groups: localized, segmental, indeterminate, and multifocal hemangiomas [9]
Summary
Infantile hemangiomas (IH) occur in 3% to 10% of infants [1]. Not all IH need treatment as IH have proliferative phase and spontaneous regression phase, and most IH can regress spontaneously. IH that can cause disfigurement and serious complications need treatment [2]. Oral propranolol is widely used in treating complicated IH [3]. The efficacy of propranolol on IH varies. Some patients failed propranolol treatment [4, 5]. Though the reported propranolol-resistant IH were rare, it is troublesome for patients who fail propranolol treatment as they often need to receive other individualized treatments such as surgical therapy [6], laser therapy [7], or injection of bleomycin [8]
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