CYP19a1基因的单核苷酸多态性与中国汉族成人寻常型痤疮的关联研究

发布时间：2019-06-14 02:18

【摘要】：研究背景 寻常型痤疮是一种常见的累及毛囊皮脂腺的慢性炎症性疾病。雄激素在痤疮发生过程中起着至关重要的作用,但其具体机制至今仍不十分明了。已有两个雄激素合成酶和雄激素受体的编码基因的多态性被证明和痤疮的发病有关。芳香化酶可将雄激素转化为雌激素,并可在皮脂腺表达。CYP19a1为编码此酶的基因,该基因序列的变异可能会影响芳香化酶的表达,进而影响雄雌激素的比例,最终导致痤疮的发生。 目的 初步探索CYP19a1基因的单核苷酸多态性与中国汉族成人寻常型痤疮发病、严重程度的关系。 方法 本研究共纳入了309例Pillsbury I-IV°的患者,均为中国华东地区汉族人群,分为轻度组(I°，，99例)和中重度组(Ⅱ-Ⅳ。,210例)。从患者外周静脉血中抽取DNA组,多重PCR获取目的基因片段后,采用SNaPshot分型技术检测CYP19al基因上的10个候选SNP位点的基因型,对比其分布频率在两组患者中的差异,并进行单倍型分析,统计分析采用SPSS16.0、Unphase、Hapstata等软件。 结果 1.rs6493497位点不符合Hardy-Weinberg平衡检验(轻度组p=2.659e-08,中重度组p=3.097e-11),将其剔除。 2.rs28892002位点(总基因频率为CC54.7%,CT38.2%,CT7.1%)的基因频率在轻度组和中重度组之间存在显著差异(p值0.05)。显性遗传模式下,CC基因型的分布频率在中重度组(58.6%)显著高于轻度组(46.5%)(p=0.046),OR=0.614,95%CI=0.379-0.993；相乘遗传模式下,等位基因T的分布频率在中重度组(23.8%)显著低于轻度组(31.3%)(p=0.048),OR=0.685,95%CI=0.471-0.997。余SNP位点基因频率分布两组间未得到阳性结果。 3.连锁不平衡结果显示, rs2255192-rs4646-rs10064-rs700519间rs2414096-rs4775936间、rs28892002-rs752760间有着良好的连锁不平衡效应,单倍型分析显示,rs2255192-rs4646-rs10064-rs700519这组单倍型在显性模式下,其C-C-A-C、T-C-A-C基因型在两组间分布有统计学差异,P值分别为0.0000、0.0216,OR值分别为5.0198和2.0707。 结论 结果提示,中国汉族人群中,CYP19a1基因上的rs28892002位点CC野生纯合子基因型可能增加中重度寻常型痤疮的患病风险；rs2255192-rs4646-rs10064-rs700519这组单倍型在显性模式下,其C-C-A-C、T-C-A-C可能减少中重度寻常型痤疮的患病风险。
[Abstract]:Background Acne vulgaris is a common chronic inflammatory disease involving sebaceous gland of hair follicles. Androgen plays an important role in acne, but its specific mechanism is still not very clear. The polymorphism of two genes encoding androgen synthase and androgen receptor has been proved to be associated with acne. Aromatase can convert androgen into estrogen and can be expressed in sebaceous gland. CYP19a1 is the gene encoding this enzyme, and the variation of this gene sequence may affect the expression of aromase, and then affect the proportion of androgen, and eventually lead to acne. Objective to explore the relationship between single nucleotide polymorphism of CYP19a1 gene and the severity and severity of acne vulgaris in Chinese Han adults. Methods A total of 309 patients with Pillsbury I-IV 掳were divided into mild group (I 掳, 99 cases) and moderate to severe group (II-IV., 210 cases). The DNA group was extracted from the peripheral venous blood of the patients. After the target gene fragments were obtained by multiplex PCR, the genotypes of 10 candidate SNP loci on the CYP19al gene were detected by SNaPshot typing technique, and the distribution frequencies were compared between the two groups. Haplotype analysis was carried out, and SPSS16.0,Unphase,Hapstata and other software were used for statistical analysis. Results the 1.rs6493497 locus was not in accordance with Hardy-Weinberg balance test (p 鈮

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