CYP19A1基因的单核苷酸多态性及AR基因CAG重复序列与中国汉族人群女性型秃发的关联研究

发布时间：2019-04-27 17:24

【摘要】：研究背景女性型秃发(female pattern hair loss, FPHL)是常见的女性毛发疾病,表现为头顶或顶前区头发密度的弥漫性降低,部分患者可伴有前发际线的后移。女性型秃发的病因除遗传因素外还包括雄激素升高、缺铁以及代谢异常等,其中雄激素的作用尤为令人关注,雄激素与毛囊雄激素受体结合后可使毛囊发生萎缩和退化,CYP19A1基因以及雄激素受体(androgen receptor, AR)基因在调节女性体内雄激素代谢及发挥作用中起到重要作用。目的探讨CYP19A1基因的单核苷酸多态性及AR基因CAG重复序列与中国汉族人群女性型秃发的关联性。方法研究对象为中国汉族200例女性型秃发患者(Ludwig II级142例,LudwigⅢ级58例)和200例健康对照,抽取外周血后分离纯化出基因组DNA,采用PCR技术扩增目的基因后进行测序,分别采用SNaPshot分型技术检测CYP19A1基因候选SNP位点的基因型,荧光标记扩增产物长度多态分析方法分析CAG重复序列的多态性。结果1.所有位点均符合Hardy-Weinberg平衡检验。2. rs6493497、rs7176005的等位基因频率在病例组和正常对照组之间存在显著差异(p=0.001)：对于rs6493497位点,病例组(A=62,G=338),对照组(A=100,G=300),p=0.001；对于rs7176005位点,病例组(T=62,C=338),对照组(T=100,C=300),p=0.001；在基因型的分析中,rs6493497、rs7176005的基因型分布在病例组和正常对照组之间存在显著差异(p=0.003)：对于rs6493497位点,病例组(AA=6,AG=50,GG=144),对照组(AA=12,AG=76,GG=112),p=0.003；对于rs7176005位点,病例组(TT=6, CT=50, CC=144)对照组(TT=6, CT=50,CC=144), p=0.003。3. rs6493497、rs7176005的等位基因频率在中度组和重度组之间存在显著差异(p=0.006),对于rs6493497位点,中度组(A=53,G=231),重度组(A=9,G=107),p=0.006；对于rs7176005位点,中度组(T=53,C=231),重度组(T=9,C=107),p=0.006；在基因型的分析中,rs6493497、rs7176005的基因型分布在中度组和重度对照组之间存在显著差异(p=0.028)：对于rs6493497位点,中度组(AA=6,AG=41,GG=95),重度组(AA=0,AG=9,GG=49), p=0.028;对于rs7176005位点,中度组(TT=6,CT=41,CC=95),重度组(TT=0,CT=9,CC=49), p=0.028。4.连锁不平衡结果显示,rs6493497、rs7176005间连锁完全不平衡(D’=1,r2=1)。5.余SNP位点基因频率及基因型分布在两组间未得到阳性结果。6.病例组和对照组的AR基因CAG重复均数分别为23.73±2.04和23.90±2.13,两组之间差异无统计学意义(p=0.481)；Ludwig Ⅱ级及Ludwig Ⅲ级病例组的CAG重复均数分别为23.60±1.92和24.07±2.28,两组之间差异无统计学意义(p=0.164)。结论CYP19A1基因rs6493497、rs7176005位点与中国汉族人群女性型秃发相关,其GG、CC野生纯合子基因型可能增加女性型秃发的患病风险；AR基因CAG重复序列与中国汉族人群女性型秃发无相关性。
[Abstract]:Background female alopecia (female pattern hair loss, FPHL) is a common female hair disease characterized by diffuse decrease of hair density in the head or anterior parietal region and some patients may be accompanied by the backward shift of the forehair line. In addition to genetic factors, the causes of female alopecia include increased androgen, iron deficiency and abnormal metabolism, among which the role of androgen is of particular concern, androgen binding with androgen receptor in hair follicles can lead to atrophy and degeneration of hair follicles. CYP19A1 gene and androgen receptor (androgen receptor, AR) gene play an important role in regulating androgen metabolism in women. Objective to investigate the association between single nucleotide polymorphism of CYP19A1 gene and CAG repeats of AR gene and female alopecia in Chinese Han population. Methods two hundred female alopecia patients (Ludwig II grade 142, Ludwig 鈪，

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