背景:特应性皮炎(AD)是最常见的炎症性皮肤病,以表皮屏障功能受损和免疫反应改变为特征,两者都受到维生素D缺乏的影响。VDR和CYP24A1中的单核苷酸多态性(SNP)先前已与AD相关。
目的:我们试图描述诊断为AD的儿童VDR和CYP24A1多态性与维生素D和脂质生化特征之间的关联。
方法:本研究共纳入246名参与者(143名AD患者和103名健康对照者)。VDR(rs2239185,rs1544410,rs7975232,rs2238136,rs3782905,rs2239179,rs1540339,rs2107301,rs2239182和rs731236)和CYP24A1(rs2248359和血清钙水平,磷,测量了维生素D,并测定了生化脂质谱。
结果:在VDRSNP中,rs2239182对AD的发展具有保护作用,而rs2238136被确定为AD的危险因素。GCC单倍型(rs2239185-G,rs1540339-C,和rs2238136-C)似乎可以防止AD的发展。rs2239182-CC与较高的25(OH)D浓度相关,而rs2238136-TT,rs2239185-GA,rs2248359-TT存在于大部分血清维生素D缺乏患者中。rs2239185-AA,rs2239182-CC,rs1540339-CC与较高的血清总胆固醇相关;rs2239182-TT与较低的低密度脂蛋白胆固醇相关;rs2239182-TC与较低的高密度脂蛋白胆固醇相关.CYP24A1SNP(rs2296241-AA和rs2248359-TT)均与较高的高密度脂蛋白胆固醇水平相关。
结论:VDRSNPrs2238136是AD和VDR和CYP24A1中其他SNP的危险因素,这可能导致影响AD风险的生化参数的改变。我们的发现突出了AD的复杂遗传基础,并表明不同遗传因素之间的相互关系可以导致维生素D代谢或脂质分布的改变。这反过来可能会影响AD的发展。
BACKGROUND: Atopic dermatitis (AD) is the most prevalent inflammatory skin disorder, characterized by impaired epidermal barrier function and an altered immune response, both of which are influenced by vitamin D deficiency. Single-nucleotide polymorphisms (SNPs) in VDR and CYP24A1 have been previously associated with AD.
OBJECTIVE: We sought to characterize the associations between the VDR and CYP24A1 polymorphisms and the vitamin D and lipid
biochemical profile in children diagnosed with AD.
METHODS: A total of 246 participants (143 patients with AD and 103 healthy controls) were enrolled in this study. Genotyping for polymorphisms in VDR (rs2239185, rs1544410, rs7975232, rs2238136, rs3782905, rs2239179, rs1540339, rs2107301, rs2239182, and rs731236) and CYP24A1 (rs2248359 and rs2296241) was performed by allele-specific polymerase chain reaction using integrated fluidic circuit technology. Serum levels of calcium, phosphorus, and vitamin D were measured, and the
biochemical lipid profile was determined.
RESULTS: Among VDR SNPs, rs2239182 exerted a protective effect against the development of AD, whereas rs2238136 was identified as a risk factor for AD. The GCC haplotype (rs2239185-G, rs1540339-C, and rs2238136-C) appeared to protect against the development of AD. rs2239182-CC was associated with higher 25(OH)D concentrations, whereas rs2238136-TT, rs2239185-GA, and rs2248359-TT were present in a large proportion of patients with serum vitamin D deficiency. rs2239185-AA, rs2239182-CC, and rs1540339-CC were associated with higher serum total cholesterol; rs2239182-TT was associated with lower low-density lipoprotein cholesterol; and rs2239182-TC with lower high-density lipoprotein cholesterol. Both CYP24A1 SNPs (rs2296241-AA and rs2248359-TT) were associated with higher high-density lipoprotein cholesterol levels.
CONCLUSIONS: The VDR SNP rs2238136 is a risk factor for AD and other SNPs in VDR and CYP24A1, which may lead to alterations in
biochemical parameters that influence the risk of AD. Our findings highlight the complex genetic basis to AD and indicate that interrelationships between different genetic factors can lead to alterations in vitamin D metabolism or lipid profiles, which in turn may influence the development of AD.