Frizzled-related proteins 4 (SFRP4) rs1802073G allele predicts the elevated serum lipid levels during acitretin treatment in psoriatic patients from Hunan, China

Background Acitretin is a second-generation synthetic retinoid, and is widely used for treating the severe psoriasis vulgaris. However, it should be chosen with caution for its cardiovascular risk, and it is reported that acitretin may increase the serum lipids. The purpose of this study is to investigate the relationship between the Frizzled-related proteins 4 (SFRP4) rs1802073 polymorphism and the changes of serum lipids in Chinese psoriatic patients during the treatment with acitretin. Methods In our study, 100 psoriatic patients were recruited systematically treated with acitretin (30 mg/day) for at least eight weeks. Data of the patients’ demographic and clinical characteristics and the results of serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were collected pre- and post-treatment. Results A total of 84 psoriatic patients were enrolled and divided into three groups by SFRP4 rs1802073 genotypes. The patients who carried with TT genotype had maintained levels of TG and LDL-C after acitretin treatment, while patients with GG/GT genotypes had significantly elevated levels of serum TG and LDL-C compared to the TT genotype (ΔTG%: 27.53 ± 59.13 vs −1.47 ± 37.79, p = 0.026, ΔLDL-C%: 10.62 ± 26.57 vs −1.29 ± 17.07, p = 0.042). The association of rs1802073 with TG and LDL-C profiles remained significant after adjusting for age, gender, and body mass index. Although without significance, the pre-post change in serum level of TC across rs1802073 GG/GT genotypes demonstrated a trend similar to TG and LDL, and the serum level of HDL-C demonstrated a trend opposite to TG, TC and LDL. Conclusions Our results demonstrated that SFRP4 rs1802073 polymorphism was found to be associated with elevated serum lipid levels after acitretin treatment, and it may serve as a genetic marker of safe and precise treatment for individual psoriatic patients.

[1]  T. Celik,et al.  Psoriasis treatment should be stratified in order to better assess the cardiovascular event rates , 2013, Journal of internal medicine.

[2]  T. Martin,et al.  Retinoic acid receptor signalling directly regulates osteoblast and adipocyte differentiation from mesenchymal progenitor cells , 2017, Experimental cell research.

[3]  J. Li,et al.  Whole Exome Sequencing in Psoriasis Patients Contributes to Studies of Acitretin Treatment Difference , 2017, International journal of molecular sciences.

[4]  S. Dogra,et al.  Acitretin in psoriasis: an evolving scenario , 2014, International journal of dermatology.

[5]  B. Thiers Pathogenesis and clinical features of psoriasis , 2008 .

[6]  Hoon Kim,et al.  Association between polymorphisms in Wnt signaling pathway genes and bone mineral density in postmenopausal Korean women , 2010, Menopause.

[7]  R. Kibbey,et al.  Impact of gain-of-function mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) on glucose and lipid homeostasis , 2017, Osteoporosis International.

[8]  J. Tao,et al.  The expression of mCTLA-4 in skin lesion inversely correlates with the severity of psoriasis. , 2017, Journal of dermatological science.

[9]  L. Badimón,et al.  LRP5 and plasma cholesterol levels modulate the canonical Wnt pathway in peripheral blood leukocytes , 2015, Immunology and cell biology.

[10]  Z. Rahimi,et al.  Paraoxonase 1 (PON1) 55 polymorphism, lipid profiles and psoriasis , 2012, The British journal of dermatology.

[11]  A. Vaisi-Raygani,et al.  Antioxidant status in patients with psoriasis , 2014, Cell biochemistry and function.

[12]  Kendra S. Carmon,et al.  Secreted Frizzled-Related Protein 4 Regulates Two Wnt7a Signaling Pathways and Inhibits Proliferation in Endometrial Cancer Cells , 2008, Molecular Cancer Research.

[13]  Liangdan Sun,et al.  A miRNA-492 binding-site polymorphism in BSG (basigin) confers risk to psoriasis in Central South Chinese population , 2011, Human Genetics.

[14]  A. Burden,et al.  Apolipoprotein E gene polymorphisms are associated with psoriasis but do not determine disease response to acitretin , 2006, The British journal of dermatology.

[15]  J. Waalen,et al.  Acitretin in psoriasis: an overview of adverse effects. , 1999, Journal of the American Academy of Dermatology.

[16]  N. Sarrafzadegan,et al.  Mutation in EGFP Domain of LDL Receptor-Related Protein 6 Impairs Cellular LDL Clearance , 2008, Circulation research.

[17]  C. Zouboulis,et al.  Current Use and Future Potential Role of Retinoids in Dermatology , 1997, Drugs.

[18]  Shuangyuan Zhou,et al.  CD147 promotes MTX resistance by immune cells through up-regulating ABCG2 expression and function. , 2013, Journal of dermatological science.

[19]  A. Bowcock The genetics of psoriasis and autoimmunity. , 2005, Annual review of genomics and human genetics.

[20]  T. Hamilton,et al.  Acitretin improves psoriasis in a dose-dependent fashion. , 1988, Journal of the American Academy of Dermatology.

[21]  R. Dahiya,et al.  Wnt antagonist gene polymorphisms and renal cancer , 2009, Cancer.

[22]  Yanqiong Zhang,et al.  Pravastatin prevents steroid-induced osteonecrosis in rats by suppressing PPARγ expression and activating Wnt signaling pathway , 2014, Experimental biology and medicine.

[23]  G. Johnson,et al.  Role of the intracellular domains of LRP5 and LRP6 in activating the Wnt canonical pathway , 2005, Journal of cellular biochemistry.

[24]  N. Samani,et al.  A Common Variant in Low-Density Lipoprotein Receptor–Related Protein 6 Gene (LRP6) Is Associated With LDL-Cholesterol , 2009, Arteriosclerosis, thrombosis, and vascular biology.

[25]  M. Ling Acitretin: optimal dosing strategies. , 1999, Journal of the American Academy of Dermatology.

[26]  Liuda Ziaugra,et al.  SNP Genotyping Using the Sequenom MassARRAY iPLEX Platform , 2009, Current protocols in human genetics.

[27]  Jianglin Zhang,et al.  Four polymorphisms of VEGF (+405C>G, -460T>C, -2578C>A, and -1154G>A) in susceptibility to psoriasis: a meta-analysis. , 2014, DNA and cell biology.

[28]  A. Ormerod,et al.  British Association of Dermatologists guidelines on the efficacy and use of acitretin in dermatology , 2010, The British journal of dermatology.

[29]  P. Andrews,et al.  Expression of Wnt and Notch pathway genes in a pluripotent human embryonal carcinoma cell line and embryonic stem cells , 2003, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[30]  G. Go,et al.  Low-Density Lipoprotein Receptor (LDLR) Family Orchestrates Cholesterol Homeostasis , 2012, The Yale journal of biology and medicine.

[31]  Mark Lebwohl,et al.  Psoriasis , 1906, The Lancet.

[32]  J. Geiger,et al.  Treatment of severe psoriasis with etretin (RO 10‐1670) , 1987, The British journal of dermatology.

[33]  W. Cao,et al.  Acitretin exerted a greater influence on T‐helper (Th)1 and Th17 than on Th2 cells in treatment of psoriasis vulgaris , 2012, The Journal of dermatology.